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PODIUM PRESENTATIONS Objective Recent studies have suggested that the subchondral bone P1 metabolism is intimately involved in cartilage degradation in osteoarthritis Autoantibodies to Heat Shock Protein 60 (hsp60) Promote Thrombus (OA). Bone remodelling is tightly regulated by a molecular triad: Formation in a Murine Model of Arterial Thrombosis OPG/RANK/RANKL. RANKL enhances osteoclastogenesis via interaction Melanie Dieude (Division of Rheumatology, The Research Institute of the with its receptor RANK, whereas OPG inhibits this osteoclastogenesis by act- McGill University Health Centre), Marc-Antoine Gillis (The Montreal Heart ing as a soluble RANKL receptor competitor. Depending on the low or high Institute, University of Montreal, Montreal), Jean-Francois Theoret (The level of PGE2, human OA subchondral osteoblasts can be discriminated into Montreal Heart Institute, University of Montreal, Montreal), Jerrold S. Levine two subpopulations: low (L) or high (H), respectively. (Section of Nephrology, University of Illinois at Chicago, Chicago, USA), Methods We investigated the modulation of OPG and RANKL levels and Eric Thorin (The Montreal Heart Institute, University of Montreal, Montreal), RANKL1 and 3 isoforms by real-time PCR, and osteoclast formation using Yahye Merhi (The Montreal Heart Institute, University of Montreal, the pre-osteoclastic cell line RAW 264.7, comparing the effects of normal to Montreal), Joyce Rauch (Division of Rheumatology, The Research Institute each OA osteoblast subpopulation (L or H). Human knee subchondral bone of the McGill University Health Centre) was also examined histologically. Further, we determined by flow cytometry Anti-heat shock protein 60 (anti-hsp60) autoantibodies from systemic lupus on L and H OA osteoblasts the level and modulation of membranous RANKL erythematosus patients induce endothelial cell apoptosis in vitro, and are upon treatment with/without osteotropic factors. associated with an increased frequency of thrombosis in patients with lupus Results Histological analysis revealed that the L OA osteoblasts had reduced anticoagulant antibodies (Dieudé et al. Arthritis Rheum 2004). However, the subchondral bone mass compared to normal, in contrast to the H OA which mechanisms responsible for anti-hsp60 autoantibody induction and pathogen- showed an increase. The OPG/RANKL mRNA ratio was significantly esis remain unclear. decreased in L OA compared to normal or H OA, and markedly increased in Objective We aimed to study how autoantibodies to murine hsp60 could be H OA compared to normal. This was further supported by the membranous induced in nonautoimmune mice, and to determine if these autoantibodies RANKL levels which were significantly elevated in L OA compared to the H would promote thrombus formation in an in vivo model of carotid artery OA and normal cells. Moreover, L OA but not H OA cells induced a signifi- thrombosis. cantly higher level of osteoclast differentiation and formation. Experiments Methods BALC/c mice were immunized with bacterial hsp65 and Freund’s with osteotropic factors revealed that i) in L OA osteoblasts, TNF-alpha, IL- adjuvant, or adjuvant alone, to produce IgG antibodies reactive with murine 1beta, PGE2, IL-6 and Vitamin D3 significantly increased the membranous hsp60 or control antibodies respectively. Naïve BALB/c mice were treated RANKL level, whereas ii) in H OA none of the factors tested affected with either purified polyclonal anti-murine hsp60 IgG antibodies or control RANKL. Finally, RANKL isoforms 1 and 3 were significantly higher in the IgG 48 hours prior to inducing carotid artery injury with FeCl3. On the day L OA compared to H OA. of the experiment, mice were anesthetized and the right carotid artery was Conclusion The OPG/RANKL ratio in the two human OA subchondral bone exposed. Blood flow through the carotid artery was measured using a minia- osteoblast subpopulations indicates different stages of this diseased tissue, in ture ultrasound flow probe interfaced with a flow meter and a computer-based which the L OA osteoblasts favour bone resorption. A better understanding of data acquisition program. The blood flow was monitored pre-FeCl3-induced the modulation of subchondral bone RANKL during the OA process will be injury to establish normal flow, and post-injury to follow thrombus formation. useful in the development of a specific therapeutic target. Blood flow decreased when thrombus formation occurred and stopped when the thrombus completely occluded the carotid artery. Blood was collected by P3 cardiac puncture for whole blood platelet aggregation studies. Elevated BAFF Levels Correlate with Altered B Cell Phenotypes in Results All (n=14) mice treated with anti-hsp60 antibodies developed virtual- Patients with Systemic Lupus Erythematosus ly complete occlusion of the carotid artery, with a mean blood flow of 1.86% Carolina Landolt-Marticorena (Toronto Western Research Institute), Gabriel following thrombus formation: no reperfusion was observed. In contrast, mice Bonventi (Toronto Western Research Institute), Yongchun Cai (Toronto (n=14) treated with control IgG showed greater instability of the thrombus Western Research Institute), Thulasi Unnithan (Toronto Western Research with frequent reperfusion [7/14 mice]) and a mean blood flow of 22.3% fol- Institute), Dafna Gladman (Toronto Western Research Institute), Murray lowing thrombus formation. In vitro collagen-induced platelet aggregation Urowitz (Toronto Western Research Institute), Paul R. Fortin (Toronto using blood from these mice was significantly lower in anti-hsp60-treated than Western Research Institute), Joan E. Wither (Toronto Western Research in control IgG-treated mice (mean resistance: 6.71 versus 10.38 Ohms, p = Institute) 0.017), consistent with prior in vivo activation in the anti-hsp60 mice. Objective It has been demonstrated that lupus patients have elevated serum Conclusion Our findings demonstrate that: i) anti-hsp60 autoantibodies can and RNA levels of BAFF. In transgenic mouse models, BAFF has ubiquitous be induced in nonautoimmune individuals by exposure to a bacterial antigen; effects including rescue of auto-reactive transitional B cells, enhancement of and ii) in a murine model of arterial thrombosis, passively transferred anti- T-B cell collaboration, and expansion of plasma cells. Since these changes hsp60 autoantibodies promote thrombus formation, vascular occlusion, and are similar to those observed in lupus patients, we examined whether BAFF thrombus stabilization. These data provide support for a prothrombotic role of expression correlates with alterations in the peripheral blood B cell compart- anti-hsp60 autoantibodies. Work supported by CIHR and FRSQ “Réseau en ments of lupus patients. santé cardiovasculaire”. Methods Patients (n = 58) satisfying ≥ 4 ACR criteria were recruited from the University of Toronto Lupus Clinic. Healthy controls (n =11) P2 were also recruited. Clinical and demographic information was obtained Human OA Subchondral Bone Remodelling Is Closely Dependent on for all study participants. Disease activity was measured by the RANKL Modulation SLEDAI-2K, with a score of ≥ 7 defined as high disease activity. Steeve Kwan Tat (Osteoarthritis Research Unit, University of Montreal Peripheral blood mononuclear cells from all study participants were iso- Hospital Centre, Notre-Dame Hospital), Jean-Pierre Pelletier (Osteoarthritis lated, stained with various combinations of fluorescently labeled anti- Research Unit, University of Montreal Hospital Centre, Notre-Dame bodies, and analyzed by flow cytometry. RNA was isolated from periph- Hospital), Daniel Lajeunesse (Osteoarthritis Research Unit, University of eral blood and converted to cDNA using a ABI high capacity kit. BAFF Montreal Hospital Centre, Notre-Dame Hospital), Hassan Fahmi RNA expression was measured by qRT-PCR reaction using Taqman Low (Osteoarthritis Research Unit, University of Montreal Hospital Centre, Notre- Density Arrays and normalized to a housekeeping gene (GAPDH). Dame Hospital), Nicolas Duval (Centre de Convalescence Pavillon des Statistical differences between groups where determined by the Mann- Charmilles), Johanne Martel-Pelletier (Osteoarthritis Research Unit, Whitney test. University of Montreal Hospital Centre, Notre-Dame Hospital) Results BAFF RNA expression was significantly elevated in SLE patients as

Downloaded on September 27, 2021 from www.jrheum.org compared to controls (p < 0.0001) and showed an association with high dis- Health Center), Patrick Bélisle (McGill University Health Center), Ann E. ease activity (p = 0.017). As we, and others have shown, lupus patients had Clarke (McGill University Health Center), Christian A. Pineau (McGill significantly elevated levels of pre-germinal center (p < 0.0001) and plasma University Health Center) cells (p = 0.0352) as compared to controls. In the current and previous stud- Objective Over the past three decades, in North America, the proportion of ies, we have noted a trend towards an expansion of the transitional cell com- women training in rheumatology has increased considerably, but there is con- partment in lupus patients when compared to controls. Patients were stratified cern that their academic productivity is inferior to their male counterparts. into high and low levels for each B cell population based on whether the pro- Because publication in medical journals is an important measure of academ- portion of cells was ≥ 3SD above the mean for controls. There was a signif- ic productivity, we aimed to determine the proportion of female physician- icant increase in BAFF levels in individuals with high levels of transitional (p investigators among authors of selected North American rheumatology jour- = 0.0229) and pre-germinal center B cells (p = 0.0204) but not plasma cells. nals over the past 25 years, and to evaluate its variation according to research Conclusion Expansion of the transitional and pre-germinal center cell com- area. partments in lupus patients was associated with increased levels of BAFF. Methods Original articles from Arthritis & Rheumatism and Journal of The findings suggest that BAFF plays a role in generation of these phenotypes Rheumatology were reviewed to determine the sex of both the first and the through effects on transitional cell survival and T-B cell collaboration. last listed author and the research area addressed (i.e. rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and osteoarthritis (OA)). Data P4 were collected for the years 1981, 1991, 2001 and 2006. The analysis was Early Psoriatic Arthritis: Establishing a cohort of patients with Psoriasis limited to authors from institutions located in Canada and the US. Logistic Uncomplicated by Arthritis regression was used to estimate odds ratios (OR) for the proportions of Vinod Chandran (Toronto Western Hospital), Sutharshini Shanmugarajah women authors across time and across research areas. (Toronto Western Hospital), Fawnda Pellett (Toronto Western Hospital), Results A total of 1886 original articles were reviewed and 1036 physician- Sergio Toloza (Toronto Western Hospital), Catherine Schentag (Toronto authors from institutions in Canada (17.9%) and the US (82.1%) were identi- Western Hospital), Cheryl Rosen (Toronto Western Hospital), Dafna Gladman fied. The sex was determined for 94.5% of these authors. The proportion of (Toronto Western Hospital) first authors who were women increased from 11.8% in 1981 to 36.4% in Objective To establish a cohort of patients with uncomplicated psoriasis to 2006 (OR 4.6; 95%CI 2.1-10.0), and the proportion of last authors who were study factors associated with development of PsA in patients with psoriasis. women increased from 8.0% to 21.6% (OR 3.1; 95%CI 1.3-7.4) during the Methods From January 2006, consenting patients diagnosed with psoriasis same period. In 1991, the proportion of women serving as first and last without arthritis by dermatologists were recruited from dermatology offices authors was 19.7% and 10.4% respectively, and in 2001, it was 36.0% and and phototherapy centres. They were evaluated by a rheumatologist to 21.7% respectively. When examining the different research areas, women exclude PsA using a standard protocol which included questionnaires, physi- were significantly more represented as first and last authors in SLE compared cal examination, laboratory and radiographic evaluation, if required. Serum to other research areas (SLE vs OA, OR 2.6; 95%CI 1.4-4.8, SLE vs RA, OR and DNA were collected at baseline from those found eligible. Those recruit- 2.3; 95%CI 1.5-3.5), and composed the majority of first authors in this field ed were then followed yearly or sooner if they developed symptoms of in 2001 (66.7%) and 2006 (53.3%), which constituted a large and significant inflammatory articular disease. The data obtained was compared to patients increase since 1981 (14.3%) (2001 vs 1981, OR 5.9; 95%CI 2.1-16.2, 2006 followed at the University of Toronto PsA Clinic. vs 1981, OR 4.1; 95%CI 1.5-10.9). Results To date, 247 patients were evaluated and 219 (134 males) were diag- Conclusion During the past 25 years, the proportion of women among both nosed with uncomplicated psoriasis and enrolled into the program for first and last physician-authors of original articles in rheumatology journals prospective follow-up. 28 patients (11.3%) had PsA and were excluded. The from Canada and the US has increased substantially. In addition, women are mean age at onset of psoriasis was 29 years, and the mean disease duration more represented in the research area of SLE, now predominating as first was 17 years. 89 (40.6%) reported a family history of psoriasis, 4 (1.8%) PsA, authors in this field. 8 (3.7%) inflammatory bowel disease, and 1 (0.5%) uveitis. 179 (82%) had psoriasis vulgaris, 26 (12%) guttate psoriasis and 6 (3%) had flexural psoria- POSTERS sis. 110 (50%) had psoriatic nail dystrophy. 203 (93%) had received pho- 1 totherapy, 43 (20%) had received systemic therapy (methotrexate-12, Critical Coronary Artery Stenosis and Aortitis in a Patient with cyclosporine-5, retionids-20, sulfasalazine-1, mycophenolate-1, steroids-1, Relapsing Polychondritis anti-TNF agents-6, alefacept-8, efalizumab-3). 72 (33%) had concurrent ill- Jonathan Stein (University Health Network), Peter Lee (Mount Sinai ness (45 hypertension, 7 ischaemic heart disease, 9 diabetes, 9 cancer). Hospital), Bindee Kuriya (University Health Network), Jerry Tenenbaum Compared to patients with PsA attending the University of Toronto PsA who (Mount Sinai Hospital), Lorretta Daniel (University Health Network), Jadish presented with psoriasis before PsA, there was a lower reported family histo- Butany (University Health Network), Yves Provost (University Health ry of PsA, lower prevalence of psoriatic nail dystrophy, and lower proportion Network), Tyrone David (University Health Network) was treated with systemic agents. Age at onset and duration of psoriasis was We report a case of a 35 year old man with relapsing polychondritis who similar. Out of 90 patients seen on follow up after 1 year, 5 patients were diag- developed coronary vasculitis and aortitis. Six years after presenting with ear nosed with PsA for an incidence rate of 5.5%. If all eligible patients are con- redness, swelling and pain, he presented with a 2-month history of new onset sidered the most conservative incidence would be 3.7%. All 5 patient new unstable angina. Echocardiogram showed a reduced left ventricular ejection onset PsA had psoriasis vulgaris, 3 had nail dystrophy. They had an average fraction and septal and inferior wall hypokinesis. CT angiogram revealed of 6 tender and 1 swollen joints. X-rays showed sacroiliitis in 2. proximal root aortitis and severe ostial stenosis of the left main and right coro- Conclusion A cohort of patients with uncomplicated psoriasis to study factors nary arteries. He was treated initially with high doses of corticosteroids, associated with onset of PsA has been established. The incidence of PsA in methotrexate and infliximab and then switched to oral cyclophosphamide. the first year is 5.5%. Compared to patients with PsA, these patients have Subsequent cardiac catherization showed significant aortic regurgitation. lower family history of PsA and lower prevalence of psoriatic nail dystrophy. Seven months after presentation he had triple cardiac bypass surgery, and composite replacement of the ascending aorta and aortic valve. Oral pred- P5 nisone and methotrexate were continued for his vasculitis. Increasing Proportion of Articles in North American Rheumatology Journals Authored by Women 2 Evelyne Vinet (McGill University Health Center), Simone Appenzeller Factors Associated with Physician Service Use in Systemic Sclerosis (McGill University Health Center), Lawrence Joseph (McGill University Sasha Bernatsky (McGill University), Pantelis Panopolis (UCSF), Marie

Downloaded on September 27, 2021 from www.jrheum.org Hudson (McGill University), Janet Pope (University of Western Ontario), fracture bone near the callus, in both in OC and OB. Chondrocytes from the 2 Sharon LeClerc (University of Calgary), Murray Baron (McGill University), callus express sPLA2 II and sPLA V. Fetal osteocyte (OCY) also show sig- Dave Robinson (University of Manitoba), Niall Jones (University of Alberta), nal for sPLA2 II. The sPLA2 X was not expressed in bone cells but seems to Janet Markland (University of Saskatchewan), Maysan Abu-Hakima be present in osteoid. Inhibition of cPLA2 in human OC promoted the forma- (University of Calgary), Jean-Pierre Mathieu (University of Montreal), Peter tion fillipodia and disruption of actin rings. Inhibition of iPLA2 and sPLA2 Docherty (University of Dalhousie), Nader Khalidi (McMaster University), had no effect on this parameter. The differentiation from peripheral mononu-

Evelyn Sutton (University of Dalhousie), Canadian Scleroderma Research clear blood cells in presence of a cPLA2 inhibitor increased OC formation Group CSRG (Canada) contrary to sPLA2 inhibitor, which dramatically decreased osteoclastogenesis. Objective To assess physician service use in a large sample of patients with iPLA2 does not seem to be involved in OC differentiation. Systemic Sclerosis (SSc), and determinants of the number of physician visits. Conclusion Different phospholipases A2 are present in bone cells and they Methods The Canadian Scleroderma Research Group (CSRG) currently are linked to specific functions like control of actin structure and OC differ- comprises 15 centres contributing to a national registry of adult patients with entiation. The specific expression of sPLA2 II in fetal, Paget’s disease bone SSc. Data are available regarding demographics (age, sex, self-reported race, and in bone post-fracture suggest a specific role in conditions of intense bone education, income) as well as clinical factors, such as date of disease onset remodeling and should be further considered as a possible pharmacologic and and organ involvement. Cohort registry members complete detailed question- therapeutic target. naires at baseline and annually. In our analyses, we examined data regarding 371 patients who provided information on visits to physicians, including fam- 4 ily physicians and all specialists. Controlling for demographic variables (age, GAVE Disease in a Patient with CREST. Complete Resolution After IV sex, and race/ethnicity) and scleroderma duration, in the primary analyses we CYC and Prednisone Therapy assessed the independent effects of education, co-morbidity, degree of skin Ariel Masetto (Universite de Sherbrooke), Charles Menard (Universite de involvement as well as SF-36 scores, on annual number of physician visits. In Sherbrooke), Patrick Liang (Universite de Sherbrooke), Jean-Daniel secondary analyses, we considered family physician visits only, and all other Baillargeon (Universite de Sherbrooke), specialists only, as separate outcomes. Objective Describe a successful non-conventional treatment of a gastroin- Results On average the patients reported 5.2 visits per year to specialty physi- testinal complication of scleroderma, the watermelon stomach (GAVE dis- cians (SD 4.1, median 4, range 0 to 27) and 3.7 visits per year to family physi- ease), refractory to argon plasma coagulation therapy. cians (SD 4.3, median 3, range 0 to 52). The median number of total physi- Methods Case Report and review of the literature cian visits per year was 6, and 25% of the sample reported 10 or more physi- Results We report the case of a patient with limited scleroderma and water- cian visits per year. Our linear regression models suggested the following fac- melon disease, in whom the conventional treatment with 4 sessions of argon tors as independent mediators of the number of physician visits: Aboriginal plasma coagulation was unsuccessful (maintenance of endoscopic lesions and race/ethnicity; post-secondary education; low SF-36 scores; high skin scores; iron deficiency anemia). As the patient had also a moderate pulmonary alve- and greater co-morbidity. Race/ethnicity predicted greater family physician olitis and based in a previous case report in the literature, a therapeutic trial use, not visits to other specialists. Higher education was associated with more of three monthly 1,0 gr IV cyclophosphamide (CYC), and low dose oral pred- specialist visits, but not family physician use. In sensitivity analyses adjusting nisone was made. Complete resolution of the iron deficiency anemia and the for region of residence, the links between patterns of physician use and macroscopic endoscopic antral ectasies were observed after the third pulse of race/ethnicity and higher education remained. No interactions were seen CYC, when the therapy was discontinued. A discret improvement in lung among demographic and clinical factors. function was also observed. Four months after the interruption of treatment Conclusion We found evidence of independent relationships between higher the haemoglobine’s level remained stable. physician visits and poor physical component scores (on the SF-36 health- Conclusion The use of a short term cyclophosphamide /steroids treatment related quality of life measure) and with higher skin scores. Further work to could be an alternative therapy to patients with watermelon stomach associat- establish the economic impact of SSc in Canada is ongoing. Our current ed with scleroderma refractory to conventional treatment. hypothesis is that medical costs in SSc are driven by clinical factors such as these two variables, as well as by co-morbidity and demographics. If this 5 hypothesis is borne out, this will lead to even stronger arguments for the Validation of a Prediction Rule for Development of Rheumatoid Arthritis importance of effective interventions to limit the sequelae of this disabling Among Patients with Early Undifferentiated Arthritis disease. Bindee Kuriya (University of Toronto), Carly Cheng (University of Toronto), Maggie Chen (University of Toronto), Vivian Bykerk (University of Toronto) 3 Objective To validate a current prediction rule for development of rheuma- Phospholipase A2 in Bone’s Cells: Implication in Bone Pathologies and toid arthritis (RA) in patients with early undifferentiated arthritis (UA). Fracture Methods The prediction rule developed by the Leiden Early Arthritis Clinic Hugues Allard-Chamard (Université de Sherbrooke), Philippe Dufort (1), was applied to patients with UA enrolled in the Toronto Early Arthritis (Université de Sherbrooke), Artur José de Brum-Fernandes (Université de Cohort. The prediction rule consists of 9 clinical variables which are scored Sherbrooke) (range 0-14). Higher scores (>8) reflect an increased risk of developing RA. Objective Our goal was to determine the localization of isoforms of phos- All patients with at least 6 months of follow up were selected and the predic- pholipase A2 in normal, pathological and post fracture bone and to determine tion rule was applied to baseline characteristics. Progression to RA or anoth- their role on bone cells metabolism. er diagnosis was determined at 6 months. Patients who developed RA were Methods Immunohistochemistry was performed on bone slices from bone compared to those who did not using the chi-square test for nominal variables biopsies of human pathologic bone or rat tibia bone 7 days after fracture using and Student’s t-test for continuous variables. the avidin/biotin system. Inhibition of phospholipase A2 on actin remodeling (1) van der Helm-van Mil, AHM et al. A prediction rule for disease outcome and osteoclast (OC) differentiation was performed using a model of OC dif- in patients with recent-onset undifferentiated arthritis. Arthritis & ferentiated from peripheral mononuclear blood cells incubated in the presence Rheumatism. 2007;56(2): 433-440. of M-CSF 10µg/ml and RANKL 30µg/ml for 21 days. Results The study population consisted of 105 patients. By 6 months of fol-

Results Immunohistochemistry showed that cPLA2 and iPLA2 were low up, 80 (76%) patients with UA developed RA while 25 (24%) developed expressed in both human osteoblasts (OB) and OCs from normal, pathologic another rheumatologic diagnosis. In a univariate analysis, the number of ten- (osteoporosis, osteoarthritis, Paget’s disease) and post-fracture bone. The der and swollen joints, RF positivity, anti-CCP positivity, poor functional sta- sPLA2 II was expressed only in fetal bone, Paget’s disease bones and post- tus and high disease activity were significantly associated with development

Downloaded on September 27, 2021 from www.jrheum.org of RA (p < 0.01). No patients with a score of < 3.0 progressed to RA while who continue to have moderate/severe pain despite adequate treatment all patients scoring > 9 did experience progression to RA. Among progres- (NSAIDs/DMARDs/biologics), only 52.2% agreed with the use of opioid sors, the median prediction score was 8.0 (IQR 6.9-9.3) while non-progres- analgesics for these sufferers. Respondents felt that opioid side effects sors had a median score of 5.1 (IQR 3.8-6.2). Using these cutoffs, 18 (75%) (drowsiness, fatigue, constipation) (89.1%), concerns re addiction/abuse/ patients with scores < 5 did not develop RA while 40 (98%) of patients with diversion (82.6%), and respiratory depression (67.2%) should limit the use of scores > 8 did develop RA. Sixty five percent of UA patients scored between opioids. Of those clinicians who disagreed with the use of opioids, 77.3% 5 and 8 with the majority (81%) having confirmed RA by 6 months. still prescribed opioids for their patients. Significant demographic differences Conclusion High scores in our UA cohort predicted those who developed RA were found in attitudes about pain management and the use of opioids. by 6 months. Baseline scores of > 8 correspond with higher rates of progres- Clinicians with less than 20 years experience wrote fewer opioid prescriptions sion while scores < 5 decrease the chance of an RA diagnosis, validating the (p=0.0096) and felt less knowledgeable (p=0.0067) and less comfortable original Leiden prediction model. Patients with intermediary scores between (p=0.011) about prescribing opioids, especially controlled-release opioids 5 and 8 still have a high chance of progression to RA and further research (p=0.0081). Rheumatologists with academic appointments saw fewer new should focus on how to better predict disease outcome in this group to mini- (p<0.0001) and follow-up patients (p<0.0036) complaining of moderate/ mize risks of under treatment and maximize benefits of early intervention. severe persistent pain, and attended fewer pain management CMEs (p=0.0054). Rheumatologists who had attended at least one pain management 6 course within the last year were more likely to agree that the residual pain of A Survey of Canadian Rheumatologists’ Approach to Fibromyalgia arthritis sufferers may benefit from opioids (p=0.013), were more aware of the Barry Koehler (University of British Columbia), Judy Le Page (University of use of Universal Precautions when prescribing opioids (p=0.040), and pre- British Columbia), Mary Koehler scribed controlled-release opioids more frequently (p=0.004) than those who Objective To review how members of the CRA address the concept of had not attended these events. fibromyalgia (FM), with regard to use of the diagnosis, treatment, and attri- Conclusion Ontario Rheumatologists are divided in their attitudes regarding bution of disability the use of opioids in the treatment of pain in patients with arthritis. The num- Methods Members of the CRA, both rheumatologists and trainees, were ber of years in practice, exposure to continuing education on pain manage- asked, either while attending at the annual meeting or by email, to complete ment, and concerns re opioid side effects appear to be major factors in their a questionnaire. Questions included demographics, whether or not fibromyal- decision to prescribe these analgesics. gia was used as a diagnosis and, if so, whether the ACR criteria were used, and how patients were managed. 8 Results 142 responses were received( 125 regular members, 17 trainees) out Cluster Analysis in Early Polyarthritis Patients of a possible 420(380 regular, 49 trainees). Responders were equally divided Nathalie Carrier (Centre hospitalier universitaire de Sherbrooke), Artur J. de among academic FT, academic PT, and community practitioners. 15 of the Brum-Fernandes (Centre hospitalier universitaire de Sherbrooke), Patrick total responders did not use the diagnosis of FM. There was no correlation Liang (Centre hospitalier universitaire de Sherbrooke), Pierre Cossette with years of practice nor centre of training. FM-diagnosers mainly used the (Centre hospitalier universitaire de Sherbrooke), Bernard Colin (Universite ACR criteria (106) ; however, 53 of those who did so did not rule out FM in de Sherbrooke), Henri-A. Menard (McGill University Health Centre), Gilles the presence of positive control points. Of those responders who used the Boire (Centre hospitalier universitaire de Sherbrooke) diagnosis of FM (with more than one response permitted), 76% felt that the Objective To evaluate if patients with early inflammatory arthritis (EIA) will diagnosis validated patients’ symptoms, 71% that patient understanding was distribute into groups with different outcomes at 30 months. improved, 46% felt that the diagnosis facilitated therapy and 19% that dis- Methods Consecutive adult patients evaluated at the Centre hospitalier uni- ability claims were validated. How responders dealt with disability claims, versitaire de Sherbrooke (CHUS) with synovitis affecting at least 3 joints for whether or not they used the diagnosis of FM, was remarkably similar - never at least one month and less than 12 months (median 4 months) are followed supported (27% user vs 34% not user); occasionally supported (56 vs 58%), longitudinally. Patients are treated according to current guidelines adapted to mostly or always supported (16 vs 8%). Treatment of generalized soft tissue the clinical situation. Cluster analysis was performed on 209 consecutive rheumatism, whether or not the practitioner utilized the diagnosis of FM, was patients with complete information at inclusion and at 30 months. Cluster very similar, with the majority using sleep modification of some type, exer- analysis is an exploratory method to group similar patients according to their cise, mild analgesics (NSAID or simple analgesics), and pain counselling initial characteristics. Variables at inclusion incorporated in the analysis were: (individual or multidisciplinary clinic). autoantibodies (RF, anti-CCP and anti-Sa), swollen joint counts, CRP/ESR Conclusion The majority of Canadian rheumatologists use the diagnostic levels, polymorphonuclear (PMN) counts, fulfillment of at least 4 criteria for term, fibromyalgia, for some of their patients with generalized soft tissue RA according to the ACR (ACR criteria), use of corticosteroids/DMARDs, pain. The management of this type of clinical scenario and and the physcians’ presence of erosions on hands/feet radiographs, age and sex. attitude toward disability determination are similar, whether or not the diag- Results Five subgroups were identified: 2 with better outcomes (Clusters 1 nosis of FM is used. and 4), 2 with intermediate outcomes (Clusters 2 and 3), and 1 with severe disease (Cluster 5). Patients from clusters 1 and 4 (better outcomes) rarely 7 have autoantibodies or erosions, show little evidence of systemic inflamma- Rheumatologists and Pain Management: In or Out of Our Comfort tion, and are younger (63% and 47% are 50 y.o. or younger, respectively). Zone? Patients from cluster 1, but not cluster 4, fullfill ACR criteria for RA. Patients Philip Baer, Erica Weinberg from Clusters 2 and 3 are frequently erosive at inclusion and the number of Objective To assess the opinions and current practices of rheumatologists erosions increases at 30 months, most fulfill ACR criteria, and they are older regarding the treatment of persistent pain in arthritis patients. (46% and 53% are at least 70 y.o., respectively). Patients from Cluster 2 do Methods In spring 2007, standardized questionnaires were distributed to not have antibodies, but frequently have high inflammation and anemia. Ontario rheumatologists at 2 regional rheumatology journal clubs and the Patients from Cluster 3 frequently have anti-CCP and RF (37% and 53%, annual Ontario Rheumatology Association meeting. Demographic data, opin- respectively), have high PMN counts and are frequently already treated with ions, and attitudes towards pain management and the use of opioids were steroids/DMARDs at inclusion. Finally, patients from Cluster 5 express solicited. autoantibodies, are frequently erosive, fulfill ACR criteria, and present sys- Results Of the 54 Ontario Rheumatologists contacted, 48 responses were temic inflammation. received (88.9%), representing approximately 37% of all Ontario rheumatol- Conclusion This analysis is compatible with previous observations suggest- ogists. Although 95.6% of respondents agreed that there are arthritis patients ing that EIA is more than one disease. The most powerful characteristics to

Downloaded on September 27, 2021 from www.jrheum.org define subgroups at inclusion are autoantibodies and the presence of erosions. built in to the design. The advantage of writing one’s own database is that it The better outcomes of Cluster 3 (with initial characteristics very similar to can be customised to one’s own practice, whereas commercial software rarely Cluster 5) suggest that early use of steroids or DMARDs may alter the expres- fits one’s own needs, and requires support for updates and modifications. The sion of autoantibodies and disease. A multivariate regression analysis will be potentail disadvantage is the requirement for time to make changes, and con- used to predict evolution of disease for a new patient, taking into account its fidence in the software. characteristics at inclusion. Conclusion With a small amount of knowledge of relational database design, databases are now intuitive to design, stable, and secure. They allow efficient 9 use of secretarial time and a move towards the paperless physician’s office. Audit of Adherence to Guidlines on Safe Use of NSAIDs The advantage of using one’s own system is that it can be customised amd Henry Averns (Queens University), Pip Nicolson (University of Cambridge) maintained without the expense of a software company. The potential disad- Objective To audit the safe and rational use of NSAIDs against best practice vantage is that the user needs to be comfortable in terms of understanding the standards based on the Canadian Consensus guidelines and current literature, underlying design to allow changes in form and report structure. particularly with respect to cardiovascular, gastrointestinal and renal toxicity. Methods Prospective review of 200 consecutive patients passing through the 11 rheumatology out-patient clinic (of HLA ) recording key data on cardiovas- Pyuria in Systemic Lupus Erythematosus (SLE) cular risk factors, gastrointestinal risk factors, and use of gastroprotection or Sasha Bernatsky (McGill University), Simone Appenzeller (McGill coxib where appropriate. Data were also collected on concomitant use of University), Christian A. Pineau (McGill University), Claire L. Young aspirin and SSRIs, monitoring of renal function and blood pressure. (McGill University), Ann E. Clarke (McGill University) Results 40% (73) patients were on a regular NSAID. Of NSAID users 55% Objective To characterize pyuria occurring without hematuria, in patients were high risk (according to accepted criteria) for GI bleeding. Nine per cent with SLE. of users were at high risk with no form of gastroprotection, including one with Methods We analyzed data on 281 patients from the Montreal General severe anaemia and one on warfarin. 17% of patients could not recall having Hospital (MGH) SLE registry. Microscopic urinalyses were performed using had a blood pressure (BP) check in the previous 12 months and a further 10% a freshly voided mid-stream specimen. In this study, we assessed patient vis- we failed to record BP in the clinical notes. In 67% we were able to identify its where hematuria (defined as the presence of any red blood cells in the that monitoring of renal function had taken place in the previous year. In two microscopic urinalyses) was absent. Pyruria was defined as the presence of unmonitored patients we diagnosed moderate renal failure on checking renal white blood cells > 10 per high power field. We assessed the univariate and function. Three of 18 patients on coxibs were on low dose aspirin which multivariate effects of demographic and clinical factors on the degree of potentially negates the benefit. Nine patients on a combination of diclofenac pyuria, using generalized mixed regression modeling. We reviewed the charts and misoprostol were also on a PPI. Following this audit we have instituted of the SLE patients with pyuria (without hematuria) to determine any clinical practice changes and will reaudit in 12 months. evidence of infection. Conclusion Results Of the 281 subjects, 74 had one or more episodes of pyuria in the In this audit we have demonstrated areas where improvement in patient safe- absence of hematuria; most had more than one episode. Seven (9.4%) of these ty could occur with respect to rational use of gastroprotection or coxibs, and 74 had a history of red cell casts according to ACR lupus criteria, though they monitoring of blood pressure and renal function despite these risks being currently had no hematuria. An additional twelve patients (16.2% of the 74) well known and accepted. We identified areas where prescribing was phar- had some indicator of significant proteinuria (≥ 500 mg of protein in their 24 macoeconomically unsound. We aim to repeat this audit in primary care hour urine collection, or ≥2+ proteinuria on dipstick) within the same week before planning an educational intervention. Clinical audit remains an effec- as the pyuria. Of the patients with significant proteinuria, only one had tive tool for reviewing and improving clinical practice. nephrotic-range proteinuria. An additional 31 patients (41.9% of the 74) had 150-500 mg of protein in their 24 hour urine collection, or trace proteinuria 10 on dipstick. In univariate analyses, pyuria tended to correlate with older age Use of a Relational Database in Clinical Rheumatology Practice — 12 and longer SLE duration. Other clinical variables (SLEDAI-2K, damage Years Experience scores, proteinuria, medication exposures), were very similar in patients with Henry Averns (Queens University) and without pyuria. We could not establish independent effects for any covari- Objective To present 12 years experience of use of an electronic rheumatol- ates. On chart review, none of the patients with pyuria had symptoms of a uri- ogy database, including comments on design and pitfalls. nary tract infection. Eleven had a urine culture; one was positive for hemolyt- Methods The author has developed an access and visual-basic driven rela- ic streptococcus, and three others grew mixed contaminants. tional database which records patient demographics, current medication, Conclusion Pyuria without hematuria is relatively common in SLE, and is rheumatological and other diagnoses, along with episode information, which often recurrent. Though pyuria without hematuria was not strongly related to can then be streamed in to a letter to the GP containing all information. disease activity in our sample, some patients had significant proteinuria. In DMARDs are listed separately, along with previous DMARD and reason for addition to nephritis or bacterial infection, the differential diagnosis may stopping. In addition outcome data are recorded including the EULAR core include atypical infections, or interstitial nephritis or cystitis; ongoing work data set. The database will calculate the DAS score and store this. Episode will assess this further. data including procedures and a summary sentence are recorded, and faxes to the office are stored electronically on the database. The database allows rapid 12 analysis of patient subsets, and runs parallel to the hospital electronic patient Impact of a Training Video on Learning the GALS Screening record which is unable to record some of this core data. Examination in Medical Students Results In 12 years the database has remained stable and secure. The initial Alf Cividino (McMaster University), Joanna Bostwick (McMaster work inputting data is rewarded by rapid access to information and letters to University) colleagues that are almost complete other than additional text from that Objective To assess the impact of a GALS screening examination training episode. Hospital electronic information systems lack the functionality video in medical students. required by a rheumatologist, and often cannot record some outcome data or Methods A questionnaire was given to the class of 2007 from McMaster present information in a doctor-friendly manner. With the database, identify- University’s Michael G. DeGroote School of Medicine after the OSCE exam ing core data is rapid, and these can be presented graphically. Separation of each year in Sept 2006 and April 2007. 130 participants responded to six ‘yes’ the actual data from the database is recommended; it results in safer data han- or ‘no’ questions regarding their awareness of the GALS exam and whether dling and easier back ups. Referential integrity and password protection is they had reviewed the training video. The participants answered eight state-

Downloaded on September 27, 2021 from www.jrheum.org ments using a scale from 1 (disagree) to 5 (agree) about their confidence in Objective To estimate the percentage of patients with active axial spondy- performing the GALS exam relative to other clinical exams, and the useful- loarthropathy that require a magnetic resonance imaging (MRI) scan to qual- ness of the training video in learning the screening exam. ify for anti-tumour necrosis (anti-TNF) factor treatment using the new Results The results were obtained in September 2006 and April 2007. There Canadian Rheumatology Association/Spondyloarthritis Research Consortium was a mean of ‘yes’ responses to the six questions evaluating awareness of the of Canada (CRA/SPARCC) guidelines in a Canadian tertiary care setting. GALS exam. A mean of 4.5 out of 5 was reported in the eight statements Methods Consecutive patients with established axial seronegative spondy- which assessed both the value of the training video as a learning tool, and the loarthropathy were recruited. Patients completed a Bath Ankylosing students’ confidence in performing the GALS. Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Conclusion These results indicate that McMaster students found the GALS to Functional Inquiry (BASFI) questionnaire and the erythrocyte sedimentation be a relatively simple skill to learn in their Musculoskeletal unit in medical rate (ESR) and C-reactive protein (CRP) levels were measured. Patients were school and were able to retain this knowledge in their graduating year. categorized into groups, those who would qualify for anti-TNF agents without Regardless of which specialty new medical graduates choose, they will have the an MRI, those that would require an MRI to determine eligibility and those who skills to screen for rheumatological disorders in a fast and efficient manner. would not qualify, even with active inflammation on an MRI. Results The newly developed CRA/SPARCC guidelines for the use of anti- 13 TNF therapy in seronegative spondyloarthropathy require a patient have Young Adult Rheumatic Disease Clinic: Needs Assessment and failed traditional treatment and have 2 of the following 3 criteria present: Identification of Service Gaps Through Focus Groups with Youth and 1/ Elevated CRP or ESR Their Parents 2/ Elevated BASDAI (≥ 4) Terri Lupton (University of Calgary), Paivi Miettunen (Alberta Childrens 3/ Active inflammation on MRI (spine or sacroiliac joint) Hospital), Nicole Fahlman (University of Calgary), Nicole Johnson (Alberta Of the 29 patients recruited in a one-year period, 12 (41.3%; 95% CI 25.5- Childrens Hospital), Anne Marie Crawford (University of Calgary), Carolyn 59.3%) would require an MRI to gain access to an anti-TNF agent. Johns (University of Calgary) Extrapolating published estimates of prevalence of seronegative arthritis and Objective The implementation of the Young Adult Rheumatic Disease clinic AS and assuming 1/3 will have severe resistant disease, approximately 9000 (YARD) was evaluated by performing focus groups with pre-transition and patients in Canada would require an MRI to determine eligibility for anti- post-transition youth and parents. The goals were to identify potential service TNF treatment. gaps and determine the challenges of transitioning between paediatric and Discussion The CRA/SPARCC guidelines are unique from their internation- adult health environments. al counterparts in that they do not leave room for an expert opinion in initiat- Methods A semi-structured questionnaire was developed for each of the three ing anti-TNF therapy in spondyloarthropathy. Instead they rely on 3 markers, focus groups: 1) Transitioned youth (TY), 2) Non- transitioned youth (NTY), acute phase reactants, BASDAI score and MRI. We have demonstrated that and 3) Parents (P). The questions covered the following areas: 1) perceptions this creates a significant MRI load, with such test being required in 41% of regarding patients’ specific healthcare needs 2) concerns regarding access to our study population. As Canada currently ranks 13/22 countries studied in healthcare and 3) potential scheduling conflicts. Specific questions for each terms of MRI resources per capita, access to imaging may delay treatment ini- focus group involved the following: a) assessment of the transition process tiation. To ensure timely access to anti-TNF agents for rheumatology patients, (TY); b) youth’s readiness for medical independence, independent living, and we may need to increase the resources (i.e. MRI scanners) available to vocation (P). patients, or modify the guidelines to allow for alternative methods of initiat- Results 22 individuals were recruited with 14 attending the 3 focus groups (5 ing treatment where MRI is not available within a timely period. TY, 4 NTY and 5 P). The following themes were identified: Clinic Functioning, Understanding of Disease, Medications, Adolescent 15 Development and Parent/family Involvement. While both TY and P were NSAID-Induced Collagenous Colitis: A Case Report overall satisfied with the transitioning process, the following potential service Nataliya Milman (The Ottawa Hospital), Gunnar Kraag (The Ottawa gaps (SG) and challenges (C) were identified among all focus groups: Clinic Hospital) Functioning: SG: Limited appointment options, as youth had to juggle Collagenous colitis (CC) is a rare entity characterized pathologically by coli- school/work schedules. C: Transportation and parking. Understanding of tis with thickened subepithelial collagenous band and intraepithelial infiltra- Disease: SG: Despite the patients’ attendance at a pediatric clinic prior to tion with inflammatory cells. While the cause of CC is unknown, an associ- YARD, there was a knowledge gap identified regarding disease and medica- ation with NSAID use has been noted. Here, a case will be presented that not tions (side effects, medication cost, medication access, and complimentary only supports such an association, but also suggests that cyclooxygenase-2 medications). C: Active disease prior to transitioning. Adolescent (COX2) selectivity may be protective against development of CC. Development: SG: career counseling. C: TY and NTY’s inability to navigate A 41 year old female with psoriatic arthritis developed acute watery diarrhea adult healthcare settings; emotional/psychological challenges with illness, several days after switching from celecoxib, which she has been taking for family and independance; effects of chronic illness on social life, higher edu- many years, to diclofenac. She stopped diclofenac two weeks later, and her cation, vocational success and financial security. Parent/family Involvement. diarrhea resolved. She then restarted diclofenac, and diarrhea recurred as SG: none identified. C: While P were supportive of youth independence and before. It persisted despite stopping diclofenac the second time. attending appointments independently, they were concerned about clinic Patient was seen in a gastroenterology clinic 3 months later. All investigations attendance and treatment compliance. All groups identified a need for support including colonoscopy were negative. The pathologic specimen showed groups. “marked thickening of subepithelial collagen layer, and markedly increased Conclusion In evaluating our transition clinic through focus groups, some numbers of inflammatory cells,” consistent with severe collagenous colitis. important themes have emerged. which will be considered with future plan- Patient was treated with a six-week course of budesonide, and her symptoms ning for the clinic. However, we recognized that information gained through resolved. small focus groups cannot be generalized to the larger population. Most available NSAIDs have been associated with CC. Our patient was taking celecoxib, a selective COX2 inhibitor, for many years. Her diarrhea start- 14 ed several days after she switched to diclofenac, a non-selective prostaglandin Application of the CRA/SPARCC Criteria for Anti-TNF Use in inhibitor. The cumulative effect of celecoxib followed by diclofenac is unlike- Seronegative Spondyloarthropathy: How Many MRI’s Are Needed? ly to be responsible considering that the symptoms stopped with cessation of Leticia Troppmann (University of Ottawa), Jacob Karsh (The Ottawa diclofenac and recurred with reexposure to the drug. This suggests that Hospital, Arthritis Centre) COX2 selectivity may be protective against development of CC.

Downloaded on September 27, 2021 from www.jrheum.org The reported length of NSAID use (and the dose) that is associated with the views were performed on a purposeful sub-sample of questionnaire respon- development of CC is quite variable, ranging from four weeks to over a dents. The interviews were transcribed verbatim and coded using constant decade. Our patient has been using celecoxib for several years, but symptoms comparative analysis with the goal to further clarify and confirm or discon- developed several days after switching to diclofenac. Time to resolution of firm the themes identified in the written survey responses. symptoms also appears to be variable, ranging from days to many months. Results Forty five out of 120 rheumatologists completed the questionnaire for Some patients resolve spontaneously after discontinuation of the NSAID, a response rate of 38% with 73.3% of respondents being male. From the ques- while others (like our patient) need additional treatment. It has been suggest- tionnaire data, features on history emerged which help rheumatologists dis- ed that NSAID-related colonic injury is represented by a continuum of tinguish between inflammatory, degenerative, and chronic pain conditions. pathologies, with CC being at the severe end of the spectrum. In our patient, These included the presence of morning stiffness, distribution of joint the first exposure to diclofenac may have resulted in a reversible inflamma- involvement, presence of joint swelling, duration of disease, fatigue, extra- tion which subsided after discontinuation of the NSAID, while rechallange articular features, functional impact, age, and gelling. The physical examina- caused enough damage to start the self-perpetuating CC requiring steroid tion finding felt to be most useful was objective evidence of joint swelling. treatment. Laboratory features considered useful fell into the themes of acute phase reac- CC is uncommon, but it needs to be recognized as an important potential tants, serology, and imaging. The interviews further qualified historical fea- complication of regular NSAID use. tures. Conclusion This qualitative analysis has found key historical, physical exam- 16 ination, and laboratory features Canadian rheumatologists use to distinguish Association of MRI and Knee Pain in Osteoarthritis: A Literature between inflammatory, degenerative and chronic pain conditions. Review Furthermore, the interviews have further qualified this data. The next step is Winnie Tam (University of British Columbia/Arthritis Research Centre of to create a screening tool which will be help rheumatologists triage urgent Canada), Jolanda Cibere (University of British Columbia/Arthritis Research referrals and distinguish between inflammatory, degenerative, and chronic Centre of Canada) pain conditions. Objective To review current literature describing clinical and population- based studies associating knee pain to structural abnormalities of osteoarthri- 18 tis (OA) on magnetic resonance imaging (MRI). Incidence of Anti-Nuclear and Anti-DNA Antibody Seropositivity, and Methods A search of MEDLINE was conducted to identify English language Immunogenicity, in Patients with Rheumatoid Arthritis Treated with publications on MRI research in knee OA and pain. Analysis of the retrieved Abatacept or Infliximab publications focused on the following areas: 1) definition of knee OA and L Bessette (Centre Hospitalier Universitaire de Quebec, Quebec, Canada), M knee pain in MRI studies; 2) evaluation of study methodology; and 3) associ- Schiff (Denver Arthritis Clinic, Denver, United States), M Keiserman (School ation of knee pain with structural abnormalities in OA. of Medicine, Pontificial Catholic University, Porto Alegre, Brazil), C Results X-ray defined OA is commonly used in population-based studies and Codding (Health Research of Oklahoma, Oklahoma City, Oklahoma, United at present, no recognized MRI definition of OA exists. MRI studies initially States), S Soncharoen (Arthritis and Osteoporosis Center, Flowood, concentrated on cartilage assessment, but an increasing number of studies Mississippi, United States), A Berman (Centro Medico Privado de have examined the correlation of structural findings with OA pain and its Reumatologia, Tucuman, Argentina), S Nayiager (St. Augustine’s Medical structural progression. Reported associations between MR imaging findings Centre, Durban, South Africa), C Saldate (Centro de Investigacion des and knee pain have been found in joint effusion, synovial thickening, bone Noroeste, Tiuana, Mexico), R Aranda (Bristol-Myers Squibb, Princeton, New marrow edema, osteophytes and minimal cartilaginous lesions. However, Jersey, United States), H Becker (Bristol-Myers Squibb, Princeton, New mixed results in these areas continue to cause disagreement regarding the Jersey, United States), C Lin (Bristol-Myers Squibb, Hopewell, New Jersey, exact source of knee pain in patients with OA. Although the literature shows United States), PLN Cornet (Bristol-Myers Squibb, Shanghai, China), M studies associating the presence of pain and its severity with MRI features Dougados (Hopital Cochin, Paris, France) such as bone marrow edema, only a few studies have provided a systematic Objective To examine the incidence of anti-nuclear (ANA) and anti-DNA description of knee pain location in OA using a self-reported knee pain dia- antibodies and immunogenicity associated with abatacept or infliximab. gram, looking into different patterns of knee pain expression. Results 156, 165 and 110 pts were randomized and treated with abatacept, Conclusion Controversy remains about the causes of knee pain in patients infliximab and placebo, respectively. At randomization, demographic and with OA. The rapid advancements in MR imaging technology and the clinical characteristics were similar across groups. At Day 197, abatacept- improvement in reliable methods for evaluating structural MRI features has treated patients were less likely to develop ANA and anti-DNA antibodies contributed to an improved understanding of possible causes of OA knee pain. than those treated with placebo or infliximab. ANA were present in 1.7%, However, further research is needed to explore MRI-defined knee abnormal- 4.9%, and 32.2% of patients treated with abatacept, placebo, and infliximab, ities and their association with knee pain, especially for earlier stages of dis- respectively. Anti-DNA antibodies were detected in 0.8%, 4.3% and 38.6% of ease. In addition, although aspects of pain and severity have been studied, patients treated with abatacept, placebo and infliximab, respectively. At Day there is little research investigating the relationship of self-reported knee pain 365, the proportions of patients who developed ANA and anti-DNA antibod- location with structural MRI abnormalities. ies were lower with abatacept than infliximab (6.5% vs 47.7% for ANA, and 2.4% vs 47.7% for anti-DNA antibodies). Using the 2 different assays to 17 detect immunogenicity, it was found that 0% of the abatacept group devel- CARS - Phase 2 - Qualitative Analysis oped antibodies to abatacept (or the CTLA-4 portion), and 62% of the inflix- Andy Thompson (University of Western Ontario), Sara Graydon (University imab group developed anti-IFX antibodies. Autoimmune symptoms/disorders of Western Ontario) were uncommon, occurring in ≤1.3% in each group through Day 365 (abata- Objective The purpose of this study is to gain insight into the nature of infor- cept group: 2 cases [vasculitis]; infliximab group: 1 case [Sicca syndrome]; mation that rheumatologists find useful to distinguish between inflammatory, placebo group (Day 1–197): 1 case [leukocytoclastic vasculitis]). One addi- degenerative, and chronic pain conditions. tional case of keratoconjunctivitis sicca was reported in a patient who Methods A qualitative analysis was performed on questionnaire responses switched from placebo to abatacept after Day 197. from a purposeful sample of 120 Canadian rheumatologists. Information from Conclusion Although differences in assay type/sensitivity prevent a direct the questionnaires was coded using constant comparative analysis with data comparison, these data demonstrate that abatacept and infliximab exhibit dif- interpretation and category development driven by conceptual concerns in the ferent characteristics in their propensity to elicit auto-antibody seroconversion data using a grounded theory approach. Semi-structured open-ended inter- and immunogenicity. However, different profiles of ANA and anti-DNA anti-

Downloaded on September 27, 2021 from www.jrheum.org body seropositivity in infliximab- vs abatacept-treated patients did not trans- Princeton, New Jersey, United States), Y Sherrer (Center for Rheumatology, late into an increase in autoimmune diseases in either group. Immunology and Arthritis, Fort Lauderdale, Florida, United States), J Becker Patients with active RA were randomized to abatacept (~10 mg/kg every 4 (Bristol-Myers Squibb, Princeton, New Jersey, United States), M Gandhi wks), infliximab (3 mg/kg every 8 wks) or placebo (every 4 wks) following (Bristol-Myers Squibb, Mumbai, India), C Joshi (Bristol-Myers Squibb, standard loading dose protocols and using a double-dummy technique, plus Mumbai, India), R Westhovens (KU Leuven, Leuven, Belgium) MTX. Validated ELISAs assessed the immunogenicity of abatacept (1 against Objective To examine patient-level reductions in fatigue, pain and sleep prob- the whole molecule, and 1 against the cytotoxic-lymphocyte antigen-4 lems through 2 yrs in the AIM and ATTAIN trials. [CTLA-4] portion alone). The immunogenicity of infliximab was assessed Methods AIM and ATTAIN were randomized, double-blind, placebo-con- using a human anti-chimeric antibody assay (Prometheus Laboratories Inc., trolled trials of 12 and 6 months duration, respectively. Patients received a CA, US). ANA and anti-DNA antibodies were evaluated using semi-quantita- fixed dose of abatacept (~10 mg/kg, according to weight range) or placebo. tive immunofluorescence and radioimmunoassay, respectively (Quintiles Patients completing the double-blind phase were eligible to enroll in the long- Laboratories, GA, US). The incidence of positive response is presented at 6 term extension (LTE). Fatigue and pain (visual analog scale) and sleep quali- and 12 months. ty (Medical Outcomes Study Sleep Scale) were assessed in patients initially randomized to abatacept who entered the LTE. Scores ranged from 0–100 19 (higher scores indicate increased problems). Maintained Efficacy and Safety of Abatacept in Rheumatoid Arthritis Results The percentage of patients with severe levels of fatigue, pain, and Patients Receiving Background Methotrexate Through 5 Years of sleep problems decreased for patients completing 2 years of abatacept treat- Treatment ment. At baseline, 44%, 44%, and 9% of AIM patients had scores of 70–100 A Russell (University of Alberta Hospital, Edmonton, Alberta, Canada), R for fatigue, pain, and sleep problems, respectively. After 2 yrs of abatacept Westhovens (UZ Gasthuisberg, Leuven, Belgium), J Kremer (Center for treatment, percentages were reduced to 10%, 4%, and 2%, respectively. These Rheumatology, Albany, New York, United States), L Moreland (University of results represent a shift toward lower scores; at Year 2, 53%, 64%, and 49% Alabama, Birmingham, Alabama, United States), P Emery (University of reported scores of 0–30 for fatigue, pain, and sleep problems, respectively. A Leeds, Leeds, United Kingdom), T Li (Bristol-Myers Squibb, Princeton, similar trend was observed in the ATTAIN trial. At baseline, 68%, 58%, and New Jersey, United States), R Aranda (Bristol-Myers Squibb, Princeton, New 13% of patients had scores of 70–100 for fatigue, pain, and sleep problems, Jersey, United States), JC Becker (Bristol-Myers Squibb, Princeton, New respectively. After 2 yrs of abatacept treatment, percentages were reduced to Jersey, United States), C Joshi (Bristol-Myers Squibb, Mumbai, India), M 24%, 9%, and 4%. At Year 2, 33%, 51%, and 39% reported fatigue, pain, and Dougados (Rene Descartes University, Paris, France) sleep problems scores of 0–30, respectively. Objective To evaluate the long-term efficacy and safety of abatacept through Conclusion Abatacept treatment resulted in reductions of fatigue, pain, and 5 years of treatment in patients with active RA and an inadequate response to sleep problems through 2 years. By improving quality of life, abatacept pro- MTX. vides meaningful benefits to RA patients. Methods This was a long-term extension (LTE) of a 1-year, Phase IIb, dou- Fatigue and sleep problems are key concerns for RA patients. Abatacept has ble-blind (DB), placebo-controlled trial. During the randomized DB period, been shown to reduce fatigue, pain, and sleep problems using group-level patients received abatacept 10 or 2 mg/kg, or placebo on Days 1, 15 and 30, analyses of the AIM (Abatacept in Inadequate responders to Methotrexate and every 4 weeks thereafter, plus MTX. Patients completing the DB period [MTX]) and ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate could enter the LTE (all received 10 mg/kg ABA, plus MTX). Efficacy (ACR responders) trials. responses; physical function [modified (m)HAQ-DI; clinically meaningful response=reduction of ≥0.3 units]; health-related [HR] QoL [SF-36]) and 21 safety were assessed. Analyses are based on patients with data available at the Efficacy of Abatacept or Infliximab Treatment in Rheumatoid Arthritis visit of interest (as-observed). Patients with an Inadequate Response to Methotrexate: Results from a 1- Results Of 235 patients completing the DB period, 219 entered the LTE Year Double-Blind, Randomized, Placebo-Controlled Trial (abatacept 10 mg/kg=84; abatacept 2 mg/kg=68; placebo=67); 130 (59.4%) L Bessette (Centre Hospitalier Universitaire de Quebec, Quebec, Canada), J were ongoing at 5 years. Baseline RA characteristics for LTE patients were Homik (University of Alberta, Edmonton, Canada), M Dougados (Hopital similar among groups at randomization (mean disease duration: 8.2-9.9 yrs). Cochin, Paris, France), M Keiserman (Pontificial Catholic University, School Improvements in ACR responses were sustained through 4 years of the LTE of Medicine, Porto Alegre, Brazil), C Codding (Health Research of (5 years total treatment). Clinically meaningful mHAQ-DI responses (54.8% Oklahoma, Oklahoma City, United States), S Songcharoen (Arthritis and and 52.8% at 1 and 5 years, respectively) and improvements in HRQoL were Osteoporosis Center, Flowood, United States), A Berman (Centro Medico also maintained. Mean changes from baseline in SF-36 physical component Privade de Reumatologica, Tucuman, Argentina), S Nayiager (St. Augustine’s summary score were 9.66 and 9.69, and in mental component summary score Medical Centre, Durban, South Africa), C Saldate (Centro de Investigacion were 6.05 and 5.38 at 1 and 5 years, respectively. No unique safety events were del Noroeste, Tijuana, Mexico), R Aranda (Bristol-Myers Squibb, Princeton, observed during the 5-year cumulative period: incidence rates of AEs and seri- New Jersey, United States), J Becker (Bristol-Myers Squibb, Princeton, ous AEs were 374.9 and 18.9 events/100 patient years, respectively, compared United States), T Li (Bristol-Myers Squibb, Princeton, United States), C Lin with 489.7 and 20.0 events/100 patient-years during the DB period. (Bristol-Myers Squibb, Hopewell, United States), PLN Cornet (Bristol- Conclusion Abatacept 10 mg/kg for 5 yrs provided durable improvements in Myers Squibb, Shanghai, China), M Schiff (Denver Arthritis Clinic, Denver, ACR responses, physical function, and HRQoL in RA patients with an inad- United States) equate response to MTX. No unique safety events were reported during the Objective To evaluate the efficacy of abatacept and infliximab by assessing LTE. These data, along with the relatively high retention rates, confirm the disease activity andstatus(DAS28 [ESR] and EULAR criteria), physical func- sustained clinical benefit provided by selective co-stimulation modulation tion (Health Assessment Questionnaire [HAQ]), and quality of life (Short with abatacept. Form [SF]-36). Methods RA patents with an inadequate response to MTX and no prior anti- 20 TNF therapy were randomized to receive abatacept (~10 mg/kg every 4 wks), Abatacept Reduces Fatigue and Pain Severity and Sleep Problems infliximab (3 mg/kg every 8 wks), or placebo (every 4 wks) following stan- Through 2 Years in Rheumatoid Arthritis Patients in the AIM and dard loading dose protocols and using a double-dummy technique, plus MTX. ATTAIN Trials LDAS (DAS28 [ESR] ≤3.2), remission (DAS28 [ESR] <2.6), EULAR A Russell (University of Alberta Hospital, Edmonton, Alberta, Canada), M response criteria (good and moderate), HAQ responders (≥0.3 unit improve- Dougados (Hopital Cochin, Paris, France), T Li (Bristol-Myers Squibb, ment) and SF-36 scores were assessed. Statistical testing was performed on

Downloaded on September 27, 2021 from www.jrheum.org the efficacy measures comparing abatacept and infliximab with placebo at apy may improve this outcome at one and two year follow-up. We set out to Day 197. The difference between abatacept and infliximab was summarized determine if CYC treatment prevents a clinically significant decline in lung using 95% CIs at Day 365. function defined as a ≥ 10% decline in % predicted forced vital capacity Results 156, 165 and 110 patients were randomized and treated with abata- (FVC) beyond a two year follow-up. The secondary outcome measures were cept, placebo and infliximab, respectively. Patient demographics and clinical a significant decline in diffusion capacity (DLCO) defined as a ≥ 10% decline characteristics were similar across groups, with mean scores of ~1.7 for HAQ in % predicted DLCO. and 6.8 for DAS28 (ESR). At Day 197, all efficacy scores were higher with Methods This was a retrospective study in an academic referral center. SSc abatacept vs. placebo and infliximab vs. placebo. Furthermore, improvements patients were included if they received a minimum of six months of CYC in HAQ scores in the abatacept and in the treated infliximab treated patients treatment and had pulmonary function tests (PFTs) performed at two year fol- vs. placebo were significant (p=0.001 and p=0.005, respectively). Mean low-up or longer from the onset of treatment. Kaplan Meier analysis was changes in PCS and MCS were also greater with ABA vs. PBO (8.4 vs. 4.3, used to analyze this data. p<0.001; 5.1 vs. 1.6, p=0.004) and IFX vs. PBO (7.7 vs. 4.3, p=0.002; 4.3 vs. Results Of 98 CYC treated SSc patients, 37 met entry criteria. Twenty six 1.6, p=0.027). At Day 365, LDAS (35.3 vs. 22.4%, [difference of 12.9%, 95% women (70%), 11 men (30%), 27 Caucasian, 7 African American, and 3 of CI=2.1, 23.7]), remission (18.7 vs. 12.2%, [difference of 6.5%, 95% CI=–2.2, other ethnicities with a mean ± SEM age at SSc disease onset of 44.4 ± 1.9 15.2]), mean change in PCS (9.5 vs. 7.6 [difference of 1.93, 95% CI=0.02, years. The follow-up period, from start of CYC to the last follow-up PFT was 3.84]) and MCS (6.0 vs. 4.0 [difference of 1.92, 95% CI=–0.30, 4.15]), and an average of 4.8 years (range 2.3 -8.3 years). The median duration of CYC HAQ responders (57.7 vs. 52.7% [difference of 5.0%, 95% CI=–6.5, 16.5]) treatment in 22 patients with the diffuse cutaneous and 15 patients with lim- were higher with ABA vs. IFX. ited cutaneous was 1.7 years (range 6 months-6.7 years). Fourteen out of 30 Conclusion At Day 197, clinical benefits were similar with either abatacept patients (47%) had a positive anti-topoisomerase antibody. or infliximab. At Day 365, the differences in mean scores/responders for the At a median of 3.6 years (range 9 months - 8.4 years), 12/37 (32%) had a sig- evaluated clinical efficacy measures were better for abatacept than infliximab. nificant decline in percent predicted FVC of ≥ 10% from their baseline PFT, These data suggest that abatacept exhibits a more durable response than thus meeting the FVC endpoint, compared with 25/37 (68%) who had stabi- infliximab (3 mg/kg every 8 wks) through 1 year. lization of their % predicted FVC. Thirty five patients had a percent predicted DLCO at a median of 3.6 years (range 7 months - 8.4 years); 13/35 (37%) 22 met the DLCO endpoint and 22/35 (63%) remained stable. Incident Collagen Vascular Disease in Patients Presenting with Conclusion These data show the majority of SSc patients who are treated with Interstitial Lung Disease CYC for active ILD experience long-term lung function stability. However, Shikha Mittoo (University of Manitoba), Allan C. Gelber (Johns Hopkins there exists a significant subgroup, around 1/3, who continue to have lung University), Lisa Christopher-Stine (Johns Hopkins University), Maureen R. function decline despite CYC therapy. Therefore, SSc patients treated with Horton (Johns Hopkins University), Noah Lechtzin (Johns Hopkins CYC still need careful long term monitoring of their lung function. University), Sonye K. Danoff (Johns Hopkins University) Objective Several studies of interstitial lung disease (ILD) suggest that prog- 24 nosis and response to therapy are meaningfully influenced by the presence of Priority-Setting Referral Tool for Rheumatology: Literature Review an underlying collagen vascular disease (CVD). Yet, what proportion of Avril Fitzgerald (University of Calgary), Monica Cepoiu (University of patients presenting with ILD have an underlying CVD is largely unknown. Calgary), Carolyn Decoster (University of Calgary) We sought to determine the incidence and predictors of a new CVD diagno- Objective The shortage of rheumatologists and primary care physicians, the sis in an ILD referral population. breadth of rheumatology clinical practice, an increasing therapeutic arma- Methods We retrospectively studied 114 consecutive patients evaluated at the mentarium, need for earlier diagnosis and treatment for specific diagnostic Johns Hopkins Interstitial Lung Disease Clinic, with available serologic stud- categories, and the aging population have strained access to rheumatologists ies, for the development of a CVD. and contributed to increasing wait-times. A national panel of rheumatologists Results In this retrospective cohort, 75 (66%) patients had at least one posi- and primary care providers, together with international collaborators are tive autoantibody. The most common autoantibodies detected were anti- developing a tool to determine the relative urgency of patients referred to a nuclear antibody (ANA) and rheumatoid factor in 61 (54%) and 28 (25%) rheumatologist. A literature review was conducted to determine if rheuma- patients, respectively. Notably, nearly one-third of these 114 patients with tology priority-setting, triage or referral tools already existed, and to identify confirmed ILD satisfied published criteria for a CVD diagnosis. Furthermore, any established criteria or indications influencing relative urgency of referral. 17 (15%) patients were diagnosed with a new CVD as a direct consequence Methods Medline, EMBASE and Cochrane databases were searched using of their ILD evaluation. Patients with new CVD diagnosis compared to those search terms: referral, consultation, triage and either global term «rheumatol- without a new CVD diagnosis were younger; mean age at ILD presentation of ogy» or a list of specified conditions. Abstracts were assessed by two review- 51.4 years [95% confidence interval (CI) 45-58 years] and 60 years [95% CI ers using criteria to determine relevance. Citation and hand searches were 57-63], respectively (p=0.01). Moreover, an ANA ≥ 1:640 (p=0.03) and ele- done on papers selected for review. Two reviewers read all selected papers to vated levels of creatine kinase or aldolase (p≤0.001) were predictive of a new determine if they met objectives. Data were abstracted from relevant papers CVD diagnosis. using data abstraction sheets. Conclusion These findings suggest that unrecognized collagen vascular dis- Results Searches yielded 679 abstracts, of which 36 were selected to read, ease may be more common than previously appreciated among patients and 19 apers were abstracted. These were divided into 3 categories: general referred with ILD. Prompt detection and early treatment of these patients musculoskeletal (MSK) diseases (11), rheumatoid arthritis (RA) (5), and spe- may lead to improved outcomes. cific MSK diseases other than RA (3). Two general MSK papers provided guidelines for three urgency bands of referrals. One paper suggested ‘inflam- 23 matory’ conditions be referred to rheumatology, providing guidelines to dif- Long Term Effects of Cyclophosphamide Treatment on Lung Function in ferent ‘inflammatory’ conditions. Eight MSK papers discussed management Scleroderma Patients with Interstitial Lung Disease of the referral process or referral letter content. Papers on referral of early RA Shikha Mittoo (University of Manitoba), Robert A. Wise (Johns Hopkins provided evidence-based algorithms for early referral criteria, and criteria for University), Fredrick Wigley (Johns Hopkins University), Laura K. predicting probability of persistence in early RA. Three papers on other Hummers (Johns Hopkins University) rheumatologic conditions included ankylosing spondylitis, systemic lupus Objective Scleroderma (SSc) patients with active interstitial lung disease erythematosus and systemic vasculitis; only the paper on ankylosing (ILD) experience a decline in lung function; cyclophosphamide (CYC) ther- spondylitis offered criteria for early referral.

Downloaded on September 27, 2021 from www.jrheum.org Conclusion This literature review did not identify a priority-setting tool for Methods Twenty-five charts of patients with a known diagnosis of scleroder- patient referral to rheumatologists across the spectrum of diseases. ma were identified from one rheumatology clinic in Hamilton, Ontario with a Conditions at the extreme ends of the spectrum of urgency had greater con- designated interest in this diagnosis. Data was collected as early as 1999, in gruence. The next step in the tool-development process will involve a panel conjunction with the release of the WHO guidelines. Search criteria includ- of primary care providers and rheumatologists rank-ordering rheumatology ed, gender, type of scleroderma (limited vs diffuse), dates and results of case scenarios, eliciting criteria that clinicians consider in assessing urgency, doppler echocardiogram and pulmonary function tests, anti-nuclear antibody and establishing patient-related weighted criteria that serve as the bases for (ANA) status and pattern. priority-setting. Results Of twenty-five patients, twenty-one patients were female and four patients male. Nineteen patients met ACR criteria for Limited Scleroderma 25 and six for a diagnosis of Diffuse Scleroderma. Fifteen patients were ANA Long-Term Efficacy and Safety of Abatacept Through 3 Years of positive with titres ranging from 1:160-1:640. Of the ANA positive patients, Treatment in Rheumatoid Arthritis Patients in the AIM and ATTAIN six were positive for an anti-centromere pattern. Six of the twenty-five Trials patients had been referred from other area rheumatologists for further A Russell (University of Alberta Hospital, Edmonton, Alberta, Canada), J assessment. Kremer (Center for Rheumatology, Albany, New York, United States), R With respect to Doppler echocardiography, fifteen of twenty-five patients Westhovens (UZ Gasthuisberg, Leuven, Belgium), M Luggen (University of (60%) had been screened on a yearly basis. Of ten patients not receiving year- Cincinnati Medical Center, Cincinnati, Ohio, United States), R Aranda ly screening, three were followed by other rheumatologists in the city, and (Bristol-Myers Squibb, Princeton, New Jersey, United States), JC Becker three other patients had been lost to follow-up for significant lengths of time (Bristol-Myers Squibb, Princeton, New Jersey, United States), C Joshi during their care. In 2006, twenty-one of the twenty-five patients (84%) had (Bristol-Myers Squibb, Mumbai, India), M Gandhi (Bristol-Myers Squibb, Doppler echocardiography completed, with three patients having been lost to Mumbai, India), MC Genovese (Stanford University, Palo Alto, California, follow-up. Only two of these patients had elevated pulmonary pressures at United States) rest (pap >35mm Hg). Both female patients had limited scleroderma both Objective To evaluate the long-term efficacy and safety of abatacept through were ANA positive, one having centromere pattern and the other was Scl-70 3 years in the AIM (ABA in Inadequate responders to Methotrexate [MTX]) positive. and ATTAIN (ABA Trial in Treatment of Anti-TNF INadequate responders) With respect to Pulmonary Function Testing (PFT), fifteen of twenty-five trials. patients (60%) had screening on a yearly basis. All patients who had yearly Methods AIM and ATTAIN were randomized, double-blind (DB), placebo echocardiography screening had also been screened with PFTs. Of the ten (PBO)-controlled trials of 12 and 6 months duration, respectively. Patients patients receiving yearly screening, three were followed by other rheumatol- received a fixed dose of abatacept (~10 mg/kg) or placebo. AIM patients con- ogists and three had been lost to follow-up. Similar to the results of echocar- tinued with background MTX. ATTAIN patients remained on ≥1 DMARDs. diography, twenty-one of twenty-five had received screening in 2006. Four of Patients completing the DB period were eligible to enroll in the open-label twenty-five patients had DLCO < 50% predicted, consistent with pulmonary (OL) period (fixed dose of abatacept ~10 mg/kg every 4 wks plus changes potentially secondary to scleroderma. MTX/DMARDs). As-observed data were used to assess response to treatment Conclusion The creation of a specific scleroderma clinic in Hamilton has (ACR 20, 50 and 70 responses) and disease status (Disease Activity Score 28 allowed for an improved and high degree of compliance with the WHO and [DAS28]-defined remission [DAS28 <2.6, based on C-reactive protein (CRP) ACCP clinical practice guidelines for the screening of pulmonary hyperten- levels] and Low Disease Activity State [LDAS (DAS28 ≤3.2)]) in patients sion in patients with scleroderma. originally randomized to abatacept. Safety was assessed at each scheduled visit day. 27 Results A total of 433 and 219 AIM patients were randomized and treated Serious Infections in the Rheumatoid Arthritis Abatacept Clinical with abatacept or placebo; 378 and 161 of these entered the OL period, Development Program: An Updated Epidemiological Assessment respectively, with 81.6% overall ongoing at 3 years. A total of 258 and 133 D Lacaille (Arthritis Research Centre of Canada, University of British ATTAIN patients were randomized and treated with abatacept and placebo; Columbia, Vancouver, Canada), TA Simon (Global Epidemiology, Bristol- 218 and 99 entered the OL period, respectively, with 60.9% overall ongoing Myers Squibb, Hopewell, New Jersey, United States), A Smitten (School of at 3 years. In both trials, the proportion of abatacept-treated patients who were Medicine, Duke University ), M Meng (Global Biostatistics, Bristol-Myers ACR responders or achieved LDAS/DAS28 (CRP)-defined remission Squibb, Hopewell, New Jersey, United States), J Franklin (ARC increased through 3 yrs, and there was no overlap of 95% CIs from 6 months Epidemiology Unit, University of Manchester, Manchester, United to 3 years. No unique safety events were observed through 3 years of the AIM Kingdom), J Askling (Epidemiology, Karolinska University Hospital Solna, and ATTAIN trials, compared with the 12- and 6-month DB periods, Stockholm, Sweden), F Wolfe (Natl Data Bank for Rheum Dis, Arthritis Res respectively. Found and U of K, Wichita, US), S Suissa (Epidemiology, McGill University, Conclusion Abatacept provides durable improvements in treatment response Montreal, Quebec, Canada), M Hochberg (Div Rheum and Clin Immunol, U and disease status, and a consistent safety profile through 3 years in MTX of Maryland Med Center, Baltimore, United States) inadequate responders and in anti-TNF inadequate responders. Although as- Background: observed data are potentially vulnerable to the discontinuations of patients Epidemiological studies provide useful reference information to assess rare responding less well to treatment, these long-term data suggest the efficacy adverse events in clinical development programs. During the double-blind benefits of abatacept may increase over time, with no unique safety events study periods of the abatacept trials in patients with rheumatoid arthritis, there through 3 years. was a small increase in the overall incidence of serious infections in the abatacept group (3.0%) compared with the placebo group (1.9%). . 26 Objective To further assess the serious infection experience in the abatacept Adherence to Guidelines for the Detection of Pulmonary Hypertension in development program. Patients with Scleroderma Methods Analyses were performed on more than 94,000 patients ever Mark Matsos (McMaster University), Nader Khalidi (McMaster University) exposed to DMARDs in 6 RA cohorts. Age- and sex-specific IRs of hospi- Objective To determine if patients with diffuse and limited scleroderma, fol- talized infection and hospitalized pneumonia were calculated and were used lowed in outpatient rheumatology clinics in Hamilton, are adequately to estimate the expected IRs and 95% CIs in the abatacept trial population by screened for early indications of pulmonary hypertension with Doppler the method of indirect adjustment. The IRs of hospitalized infection and hos- echocardiography and pulmonary function testing on a yearly basis. pitalized pneumonia observed in the cumulative abatacept trial experience

Downloaded on September 27, 2021 from www.jrheum.org (double-blind and open-label periods) were compared to the IRs expected Conclusion Significantly more patients treated with abatacept achieved MDA based on the RA cohorts. based on both the core set definition and DAS-based definition. The presence Results A total of 4,134 trial patients were treated with abatacept for a cumu- and persistence of MDA were associated with slowing of erosion and joint lative exposure of 8,392 person–years. There were 221 hospitalized infections space narrowing, indicating discriminative and predictive validity. and 54 cases of hospitalized pneumonia. The incidence rates of hospitalized infection and hospitalized pneumonia per 100 person-years in the abatacept 29 trials were 2.72 and 0.65, respectively. This is similar to the expected IRs in Observed and Expected Malignancies in the Rheumatoid Arthritis RA cohorts. The incidence rates of hospitalized infection and hospitalized Abatacept Clinical Development Program: An Updated Epidemiological pneumonia per 100 person-years in the Norfolk Arthritis Registry (UK) were Assessment 1.41 and 0.27, respectively; in the Early Arthritis Register Cohort (Sweden) D Lacaille (University of British Columbia, Vancouver, British Columbia, 1.83 and 0.53, respectively; in the British Columbia Population-based RA Canada), TA Simon (Bristol-Myers Squibb, Hopewell, New Jersey, United Cohort (Canada) 3.00 and 0.79 respectively; in the Inpatient Register RA States), AL Smitten (Duke University School of Medicine, Durham, North cohort (Sweden) 3.92 and 1.04, respectively; and in the PharMetrics medical Carolina, United States), M Meng (Bristol-Myers Squibb, Hopewell, New and pharmacy claims database (US) 3.53 and 1.26, respectively. In the Jersey, United States), S Suissa (McGill University, Montreal, Quebec, National Data Bank for Rheumatic Diseases (US) the expected incidence rate Canada), J Askling (for the Epidemiology Study Group) (Karolinska of hospitalized pneumonia was 1.31. Institutet, Stockholm, Sweden), J Franklin (ARC Epidemiology Unit, Conclusion The occurrence of hospitalized infection and hospitalized pneu- Manchester, United Kingdom), M Hochberg (Div Rheum Clinic Immunol, U monia in the abatacept trials are consistent with expectation based on refer- of Maryland, Medical Center, Baltimore, Maryland, United State), F Wolfe ence data from RA cohorts exposed to non-biologic DMARDs. The published (National Data Bank for Rheumatologic Diseases, Witchita, Kansas, United literature suggests that RA patients are at higher risk of infection compared States) with the general population, making the RA DMARD observational cohorts Objective The objective was to compare the malignancy experience in the an appropriate reference. The overall safety of abatacept with respect to seri- RA abatacept clinical development programs (CDP) with the malignancy ous infections will continue to be monitored as part of a post-marketing sur- incidence in cohorts of RA patients treated with non-biologic DMARDs, as veillance program to increase the understanding of infection incidence rates these drugs were the predominant background therapy in the RA abatacept in RA patients in general and abatacept-treated patients, specifically. CDP. Methods Crude, age-, and sex-specific incidence rates (IRs) of prespecified 28 malignancies in the cumulative abatacept CDP (double-blind [DB] and open- Minimal Disease Activity State for Patients with Rheumatoid Arthritis label [OL] periods) were calculated. Age- and sex-specific IRs of prespecified Treated with Abatacept malignancies were computed using US general-population data from SEER GA Wells (Epidemiology and Community Medicine, University of Ottawa (USGP), and from ~94,000 RA patients ever exposed to DMARDs in 6 RA Heart Institute, Ottawa, Canada), M Boers (Clinical Epidemiology and cohorts: the British Columbia RA Cohort (Canada), the Norfolk Arthritis Biostatistics, VU University Medical Center, Amsterdam, Netherla), T Li Registry (UK), the National Data Bank for Rheumatic Diseases (US), the (Immunology, Bristol-Myers Squibb, Princeton, New Jersey, United States), Inpatient Register RA Cohort (Sweden), the Early Arthritis Register Cohort P Tugwell (Institute of Population Health, University of Ottawa, Ottawa, (Sweden), and the General Practice Research Database (UK). Age- and sex- Canada) specific malignancies from each of the RA cohorts were used to estimate the Background Two definitions for minimal disease activity (MDA) were devel- expected number in the abatacept CDP by the method of indirect adjustment. oped at OMERACT 7 (1 based on DAS28, the other on the ACR core set). The number of observed malignancies in the cumulative abatacept CDP is Objective To compare abatacept to control with respect to patients attaining compared with the expected number of malignancies based on the USGP and a state of MDA. To validate the MDA definitions by determining whether RA cohorts via standardized incidence ratios (SIR) with 95% CI. being in a state for a period of time leads to benefits in terms of functional dis- Results The cumulative abatacept experience includes a total of 4,134 abata- ability and structural damage. cept-treated RA patients representing ~8,400 person-years of exposure. Methods Two randomized controlled trials – the AIM (Abatacept in Observed IRs in the abatacept CDP were 0.61, 0.08, 0.15, and 0.06 for over- Inadequate responders to Methotrexate [MTX]) and ATTAIN (Abatacept Trial all malignancies*, breast, lung, and lymphoma, respectively. The range of IRs in Treatment of Anti-TNF INadequate responders) trials – were considered. in RA cohort were 0.81–2.3, 0.098–3.6, 0.12–0.37, and 0.07–0.13 for overall Outcomes assessed included ACR core set measures and DAS28. For the AIM malignancies*, breast, lung, and lymphoma, respectively. The range of SIRs study radiographic scores were available. The core set and DAS-based defini- in the RA cohort were 0.3–0.9, 0.2–0.8, 0.6–2.5, and 0.7–1.1 for overall tion were calculated and, for each study, the numbers of patients in the treat- malignancies*, breast, lung, and lymphoma, respectively. The CIs for the IRs, ment groups that met the definitions were compared to determine sensitivity observed and expected events based on the RA cohorts overlap. of the criteria to treatment differences and patient severity. The number of The SIRs for malignancies in the USGP cohort were 0.8, 0.4, 1.5, and 2.2 for times and first time achieving MDA were determined in the analysis of the overall malignancies*, breast, lung, and lymphoma, respectively. AIM study and compared to radiographic scores. This analysis was repeated *excluding non-melanoma skin for variations of the definitions. Conclusion Increased incidences of lung cancer and lymphoma were Results For both the ATTAIN and AIM studies, a significantly greater num- observed using the USGP as reference; the observed overall malignancies, ber of patients in the abatacept group than in the corresponding control group breast, lung, and lymphoma cancers are in the range of expected based on the met the core set (ATTAIN: 10.6% vs. 3.1%, p=0.0097; AIM: 29.0% vs. 9.2% RA DMARD cohorts. Published literature suggests that RA patients are at p<0.0001) and DAS-based definition (ATTAIN: 12.6% vs. 1.8%, p=0.007; higher risk of lung cancer and lymphoma than the USGP, making the RA AIM: 21.9% vs. 2.4%, p<0.001) of MDA. The change in total radiographic DMARD observational cohorts an appropriate reference. The overall safety of score showed a continual improvement the more often a patient was in MDA. abatacept will continue to be monitored as part of a post-marketing surveil- In particular, the changes in total score were 1.68, 1.57, 1.25, 0.80 and 0.52 lance program. for patients that were in MDA 0, 1, 2, 3, and 4 times, respectively. Both the erosion and joint space narrowing scores followed this pattern. Similarly, the 30 total score for patients who achieved MDA the first time at 12 and 3 months Targeting the IL-6 Receptor with the Monoclonal Antibody Tocilizumab were 1.19 and 0.73, respectively. The sensitivity analysis indicated that the Significantly Improves Quality of Life in Patients with Rheumatoid cutpoints chosen for the definition were reasonable and the initial node in the Arthritis definitions did not lead to substantive differences in the results. J Smolen (Medical University of Vienna and Hietzing Hospital, Vienna,

Downloaded on September 27, 2021 from www.jrheum.org Austria), C Atkins (Division of Rheumatology,and PerCuro Clinical courses (C) of RTX. The median time period between the treatment courses Research,Vancouver Island Health Authority Group, British Columbia), J was 48.7 weeks for C1-C2 and 56.2 weeks for C2-C3. Efficacy data were Rovensky (National Institute of Rheumatic Diseases, Piestany, Slovakia), C available for 57 pts who, at the time of analysis, had reached at least 24 Ramos-Remus (Research Unit for Chronic Diseases, Guadalajara, Mexico), weeks’ follow-up post-C3. Sustained efficacy was demonstrated by ACR50 in M Lucero (Hoffmann-La Roche Inc., Basel, Switzerland), T Woodworth 25%, 33%, and 33% of patients in C1, C2, and C3, respectively. ACR70 was (Roche Products Ltd, Welwyn, United Kingdom), R Alten (Schlosspark seen in 7%, 12%, and 12% in C1, C2, and C3, respectively. Remission, Clinic, University Medicine, Berlin, Germany) defined as DAS<2.6, was seen in 5%, 9%, and 14% of patients in C1, C2, and Purpose Interleukin (IL)-6 and the soluble IL-6 receptor (IL-6R) are enriched C3 groups, respectively. in the sera and synovial fluid of patients with rheumatoid arthritis (RA). Conclusion Our results show that repeated courses of RTX produce sustained Tocilizumab (TCZ) is a new humanized monoclonal antibody specific for the efficacy in pts with active RA and a previous inadequate response to DMARDs. IL-6R. Inhibiting the IL-6/IL-6R complex and disrupting downstream signaling with TCZ have been shown to reduce disease activity in RA. The aim of 32 this study was to investigate the effects of TCZ on health-related quality of Top Methotrexate Information Sites on the Internet: A Review of life (HRQOL) in RA patients. Completeness, Accuracy, Format, Reliability, Credibility, and Methods In a randomised controlled trial, 623 individuals with moderate to Readability severe RA and inadequate response to methotrexate (MTX) received 8 mg/kg Andrew Thompson (University of Western Ontario), Sara Graydon TCZ, 4 mg/kg TCZ, or placebo (PBO) every 4 weeks. Approximately 55% of (University of Western Ontario) patients were taking corticosteroids and 65% were taking NSAIDs or Cox-2 Objective The goal of this study was to explore the overall content and read- inhibitors. No other anti-rheumatic drugs were allowed, with the exception of ability characteristics of methotrexate information presented on commonly MTX. HRQOL measurements included the Health Assessment Questionnaire found English-written websites. (HAQ) and Functional Assessment of Chronic Illness Therapy-Fatigue scale Methods Identification of websites was performed using a search strategy on (FACIT- Fatigue), and the Short Form 36 Health Survey (SF-36). the popular search engine Google. The first 250 web pages were screened. Results The change from baseline to week 24 for each HRQOL parameter in Inclusion criteria included those English-written websites from authoritative TCZ-treated groups exceeded the accepted thresholds for minimal clinically sources, trusted medical, physicians, and common health related websites. important difference. TCZ-treated patients showed significant improvements Websites from pharmaceutical companies, on-line pharmacies, and where the in HAQ (baseline HAQ: TCZ 8 mg/kg 1.55; 4 mg/kg 1.64; placebo 1.55), purpose seemed to be primarily advertisements were also included. Product FACIT-Fatigue, and the SF-36 physical and mental health and vitality scores monographs or technical based web pages and web pages where the informa- (Table 1). Clinically meaningful changes for HAQ were observed at week 4 tion was clearly directed at patients with cancer were excluded. Each includ- for the TCZ 8 mg/kg and 4 mg/kg groups, but were not maintained until week ed web page was scored independently by two reviewers for completeness 20 for the PBO group. A mean change of >4 points in FACIT-Fatigue scores and accuracy, format, readability, and reliability and credibility. An overall were observed as early as week 4 in the TCZ 8 mg/kg group, week 8 in the ranking revealed the top methotrexate information web pages. TCZ 4 mg/kg group, and not until week 20 in the PBO group. Results Twenty-seven web pages were included in the analysis. The average Conclusion TCZ use resulted in clinically significant improvements in score for completeness and accuracy was 15.48 ± 3.70 (max 24) with 9 out of HRQOL, fatigue, and physical and mental functions in RA patients. These 27 pages scoring 18 (75%) or higher and the average format score was 6.00 ± results suggest that IL-6R inhibition is promising as a novel treatment for RA. 1.46 (max 8). Using the Flesch-Kincaide Grade Level, the average grade level was 10.07 ± 1.84 with 7 out of 27 websites written at a reading level less than 31 grade 8, however, no web page was scored at a grade 5 to 6 level. An overall Repeated Treatment Courses of Rituximab Produce Sustained Efficacy ranking was calculated identifying 7 web pages as appropriate sources of in Rheumatoid Arthritis Patients with an Inadequate Response to accurate and reliable methotrexate information. Disease-Modifying Anti-Rheumatic Drugs Conclusion With the enormous amount of information available on the inter- Paul Emery (Leeds General Infirmary), Majed Khraishi (Memorial net, it is important to direct patients to web pages which are complete, accu- University of Newfoundland and Nexus Clinical Research), Daniel Furst rate, readable, and credible sources of information. This study has helped to (University of California at Los Angeles), Gianfranco Ferracioli (Catholic identify those web pages which may serve the best interests of both rheuma- University, Rome, Italy), James Udell (Arthritis Group, Philadelphia, P), tologists and their patients. Ronald van Vollenhoven (Karolinska University Hospital, Stockholm, Sweden), Karen Rowe (Roche Products Ltd, Welwyn Garden City, United 33 Kingdom), Sunil Agarwal (Genentech, Inc., South San Francisco, CA), Tim Holding Me Back: Living with Arthritis While Recovering from a Stroke Shaw (Roche Products Ltd, Welwyn Garden City, United Kingdom) Jennifer Wood (University of Western Ontario), Laura Gibbs (University of Objective To provide extended evaluation of the long-term efficacy of repeat- Western Ontario), Denise Connelly (University of Western Ontario), Monica ed courses of rituximab (RTX) treatment in patients (pts) with active rheuma- Maly (University of Western Ontario) toid arthritis (RA) and a previous inadequate response to disease-modifying Objective To describe the experience of living with arthritis while recovering anti-rheumatic drugs (DMARDs). from a stroke. Methods The analyses utilized results from the September 2006 data cut of Methods This qualitative study was framed in the phenomenological tradition an ongoing open-label extension of two Phase II studies (1, 2). Pts were eli- to understand daily experiences. Participants included three men and two gible for repeat treatment if they met predefined criteria: ≥20% improvement women with self-reported arthritis who were recovering from a first stroke. in SJC and TJC and residual disease activity defined as ≥8 SJC and TJC. The Joints affected by arthritis included five knees, one lower back, and one shoul- need for repeated courses was determined by each pt’s treating physician. der. All five participants experienced left upper and lower extremity hemi- Placebo-treated pts were also eligible for entry into the extension study. All paresis, to varied degrees of impairment. A total of 14 one-on-one semi-struc- courses of RTX treatment consisted of two infusions of RTX (1000 mg x 2) tured interviews, each lasting approximately one hour, were conducted. on Days 1 and 15; prior to each infusion, all pts received 100 mg IV methyl- Interviews were audiotaped and transcribed verbatim. NVIVO 7 software prednisolone and treatment with oral glucocorticoids. All efficacy outcomes was used to facilitate analysis, as described by the modified van Kaam were assessed relative to the original pretreatment baseline. method (Moustakas, 1994). Results Out of all pts in the RTX clinical trial program, 273 with a prior inad- Results For all participants, “holding me back” was central to the experience equate response to DMARDs had been exposed to ≥1 courses of RTX (1000 of living with arthritis during stroke recovery. The participants described that mg x 2 for each course). A total of 94 of these pts had received at least 3 their recuperation following stroke was hampered by arthritis. Specifically,

Downloaded on September 27, 2021 from www.jrheum.org participants were held back by joint pain, mobility problems, heightened frus- 35 tration, and additional demands for coping. Pain from arthritis was a daily Validation of a Clinical Definition for Fragility Fracture experience. The limitations caused by pain occurred most often during phys- Jacques P. Brown (Laval University), Louis Bessette (Laval University), ical activity, such as physiotherapy exercises. The participants’ mobility prob- Sonia Jean (Institut national de santé publique du Québec), K. Shawn lems had a negative impact on their ability to physically interact with their Davison (Laval University), Michèle Beaulieu (Merck Frosst Canada), environment. For example, some participants were unable to access different Mirela Baranci (sanofi-aventis Canada), Jennifer Bessant (P & G parts of their own homes, or attend their local church. Frustration was the Pharmaceuticals Canada), Louis-Georges Ste-Marie (University of Montreal) emotional consequence of disappointing and unsuccessful physical activity, Objective The aim of this analysis was to validate a clinical definition for such as the inability to resume their hobbies. Cognitive and behavioral strate- fragility fractures: a fracture occurring spontaneously or following a minor gies were used by participants to cope with these difficult experiences. trauma, such as a fall from standing height, a fall from the sitting position or Conclusion Based on the experiences of these participants, the impact of pre- a fall from lying on a bed or a reclining deck chair from less than a meter high, morbid arthritis on stroke recovery should not be ignored. Functional recov- a fall after having missed 1 to 3 steps in a staircase, after a movement outside ery from stroke is perceived to be slowed due to the symptoms of arthritis. of the typical plane of motion, or coughing. The experience of slowed progression illustrates the need to consider the Methods Recognizing Osteoporosis and Its Consequences in Québec is an influence of arthritis on stroke recovery during acute care and rehabilitation. ongoing patient health management program aiming to improve the rate of Treatments for stroke that emphasize weight-bearing exercises or eliminate diagnosis and treatment of osteoporosis for women 50+y that have suffered a pain and/or anti-inflammatory medications may not be well tolerated by those fragility fracture. To date, 3288 women, mean age (SD) of 65.2 (10.3)y have with arthritis. Alternate forms of pharmacological treatment and modes of been recruited 0 to 16 weeks following a fracture either at cast/outpatient clin- physical rehabilitation should be considered. ic or by mail using the Health Administrative Database of the Province of Quebec and together have experienced 3485 fracture events. The hospitals 34 acting as recruiting sites for the cast/outpatient clinics cohort and the admin- Factors Influencing Diagnosis and Treatment of Osteoporosis Following istrative claims database redundantly served approximately half of the popu- a Fragility Fracture lation of the Province of Quebec. Patients were contacted by phone to answer Louis Bessette (Laval University), Jacques P. Brown (Laval University), a short questionnaire to classify them as having either experienced a fragility Sonia Jean (Institut national de santé publique du Québec), K. Shawn or traumatic fracture. Davison (Laval University), Michèle Beaulieu (Merck Frosst Canada), Results The proportion of fragility fractures increased progressively with age Mirela Baranci (sanofi-aventis Canada), Jennifer Bessant (P & G [73.8% (50-59y), 80.6% (60-69y), 85.5% (70-79y) and 92.8% (80+y)] and Pharmaceuticals Canada), Louis-Georges Ste-Marie (University of Montreal) was similar between the various types of fracture [wrist (83.0%), humeral Objective ROCQ (Recognizing Osteoporosis and Its Consequences in (76.1%), ankle (82.6%)], except for a higher proportion at the hip (93.0%), Québec) revealed that 73% of women 50y and over are not provided anti-frac- presumably because of its occurrence in older individuals. While sites com- ture therapy following fragility fracture. This study’s objectives were to deter- monly associated with decreased BMD and thus osteoporosis (ie. hip, mine predictors of osteoporosis (OP) diagnosis (DX) and treatment (TX) 6-8 humerus, wrist) contributed largely to the total number of fractures, there months after fragility fracture. were sites not generally associated with low BMD or increased incidence with Methods At phase 1, women were recruited at cast or outpatient clinics (17 aging that also had significant numbers of fragility fractures, such as the hospitals) within 16 weeks following fracture. Consenting patients were ankle. contacted by phone to answer a short questionnaire classifying them as hav- Conclusion The majority of fractures observed in this cohort of women over ing either experienced a fragility or traumatic fracture. During the first the age of 50 years were fragility fractures, regardless of site. This supports phone contact, no reference to the association between the fracture and OP the contention that fragility fractures should be defined by the trauma that and no investigation or intervention was proposed. At phase 2, 6-8 months caused the fracture, not by BMD or by including specific skeletal sites as a following fracture, women were again contacted to complete a question- catch-all for all osteoporotic fractures. The proposed clinical definition of naire on demographic features, clinical characteristics and risk factors for fragility fracture based on the underlying trauma fulfills the criteria for the OP. The DX (informed of OP and/or BMD measurement with diagnosis of classical definition without the requirement of a low BMD and should be pre- OP) and TX (bisphosphonates, raloxifene, nasal calcitonin or teriparatide) ferred in epidemiologic and clinical studies. rates of OP were determined via this questionnaire. This analysis included only women with a fragility fracture who were not receiving OP TX at 36 phase 1. Isotype Usage and Fine Specificity of Anti-Citrullunated Protein Results Of the 1273 women who completed phase 1, 1001 (79%) suffered a Antibodies and Rheumatoid Factor in First Nations RA Patients and fragility fracture; 818 were untreated at phase 1 and completed the phase 2 Their First Degree Relatives: New Insights into RA Onset questionnaire. Overall, 79% of these participants had not received a DX of Annemiek Willemze (Leiden University), Andreea Ioan-Facsinay (Leiden osteoporosis or were without OP TX at phase 2. The highest rate of DX and University), David Robinson (University of Manitoba), Christine Peschken TX occurred between 0-5 months following fracture and decreased consider- (University of Manitoba), Janet Markland (University of Saskatchewan), ably thereafter. In multivariate analyses, the results of BMD tests before or Marvin Fritzler (University of Calgary), Marianna Newkirk (McGill after the fracture event (p<0.0001) and mobility problems (p=0.03) were the University), Henri Menard (McGill University), Brenda Elias (University of only variables that influenced the DX of OP. The BMD test result was the Manitoba), Rene Toes (Leiden University), Tom Huizinga (Leiden strongest predictor (p<0.0001) of TX followed by the fracture site (hip, femur University), Hani El-Gabalawy (University of Manitoba) and pelvis; p=0.015) and vitamin D supplementation at the time of fracture Objective In a high risk First Nations (FN) population, to evaluate differences (p=0.035). All other risk factors for OP such as age, fracture history after age between RA probands (RA) and their first degree relatives (FDR) in the 40 years, family history of OP, and comorbidities didn’t influence the DX or prevalence, isotype usage, and specificity of Anti-Citrullinated Protein TX rate. No demographic characteristics, clinical features or OP risk factors Antibodies (ACPA) and rheumatoid factor (RF). were significantly associated with the decision to send women for BMD test- Methods We recruited RA (n=80) and FDR (n=204) from urban (Winnipeg, ing following fracture. Saskatoon) and rural locations (Norway House, St Theresa Point) to a longi- Conclusion Despite the evidence showing that the occurrence of a fragility tudinal study of RA onset. An FN unrelated control group (n=91) and a fracture represents a greater risk of future fragility fracture than a low BMD Caucasian control group (n=60) were tested in parallel. Serum samples from measurement, physicians based their decision to treat on BMD results and not the baseline visit were tested by custom ELISA assays for ACPA (IgG1, on the clinical event (fragility fracture). IgG2, IgG3, IgG4, IgM, IgA isotypes), RF (IgM, IgA isotypes), citrullinated

Downloaded on September 27, 2021 from www.jrheum.org fibrinogen (cit-fib), anti-Sa, and a panel of antinuclear antibodies. Samples 38 were also tested by ELISA for responses to a panel of linear peptides derived Open Label Study for Treatment of Angiography-Negative, Biopsy- from fibrinogen, vimentin, and a-enolase. Cut-off levels for ELISA were Positive Primary CNS Vasculitis in Children based on the Caucasian control samples (mean + 2SD) Clare Hutchinson (Hospital for Sick Children), Jorina Elbers (Hospital for Results Approximately 20% of the healthy FDR had ACPA (any isotype) Sick Children), William Halliday (Hospital for Sick Children), Helen compared to >90% of RA, 8% of unrelated FN controls, with IgG1 being the Branson (Hospital for Sick Children), Suzanne Laughlin (Hospital for Sick most frequent isotype. Most RA patients were positive for all 6 ACPA iso- Children), Derek Armstrong (Hospital for Sick Children), Cynthia Hawkins types while healthy FDR that were ACPA positive used mostly 1 isotype or (Hospital for Sick Children), Susanne Benseler (Hospital for Sick Children) maximum 2 (p<0.0001). IgM RF was positive 16% of FDR and 82% of RA. Objective To describe an open label treatment study of angiography-negative, In total 50-60% of RA were positive for anti-cit-fib and anti-Sa compared to biopsy-positive primary CNS vasculitis of childhood with induction therapy none of the FDR. Using the citrinullated peptides from vimentin and fibrino- including intravenous cyclophosphamide and high dose steroids, followed by gen, none of the sera from healthy FDR reacted against these peptides while maintenance therapy with azathioprine or mycophenylate mofetil. a significant proportion of RA sera recognized one or more citrullinated epi- Methods A single centre prospective cohort study of children age <18 years topes (42 % of IgG ACPA-positive patients). There was a high degree of con- diagnosed with angiography-negative, brain biopsy-positive primary CNS cordance between ACPA and RF in the RA patients (80%), but surprisingly, vasculitis between October 1998 and October 2007 was performed. Inclusion there was little concordance in the FDR (4%). Thus, in RA the presence of criteria: Diagnosis of primary CNS vasculitis of childhood (cPACNS) ACPA had an OR of 7 [95% CI 2-20] in the absence of IgM RF but an OR of according to Calabrese criteria with normal CNS angiography and positive 214 [95%CI 25-1831] in the presence of IgM RF with strong interaction brain biopsy confirming small vessel cPACNS. Exclusion criteria: a) between ACPA and IgM-RF. neonates, b) significant underlying medical conditions ie. collagen vascular Conclusion The FDR of FN RA patients have a high prevalence of ACPA diseases, hemoglobinopathies, infections, mimics (demyelination, metabolic and RF. Compared to RA, isotype usage in ACPA+ FDR is limited. The diseases) or c) lack of biopsy to confirm the diagnosis of small vessel CNS presence of antibodies to cit-fib and Sa only in RA and not FDR suggests vasculitis. Baseline patient demographics, clinical presentation, laboratory that epitope spreading and immune response maturation are associated and imaging data and biopsy histology were recorded. Children were started with disease onset after initial tolerance is broken in the pre-disease on high dose steroids plus a 6-month IV cyclophosphamide induction regi- phase. men followed by 18 month azathioprine maintenance therapy. Treatment efficacy and safety was documented. Neurological outcome was collected at 37 standardized follow up assessments using the Pediatric Stroke Outcome Waiting Times for a Rheumatology Consultation in Canada Measure (PSOM). Robert McKendry (Rheumatology Research Associates), Anh Tran Results Eighteen patients (14 F: 4 M) had a diagnosis of angiography-nega- (University of Ottawa) tive, biopsy-positive primary CNS vasculitis. The mean age at diagnosis was Objective To determine the Rheumatology Consultation (RC) Waiting Time 10.3 years. Mean follow up time was 36.2 months. Sixteen patients received (WT) for patients with Early Rheumatoid Arthritis (ERA) or Fibromyalgia 7 pulses of IV cyclophosphamide (500 - 750 mg/m2) over 6 months and high (FM). dose steroids (initial dose 2 mg/kg/day) weaned over 9 months as induction Methods Telephone (up to 4 times) the appointment booking offices/clinics therapy. Of these, 2 patients had disease refractory to the standard induction of all adult rheumatologists in the 2005 Canadian Medical Directory to protocol and required the addition of infliximab. Thus far, 14 patients have request a RC appointment for two mock-patients: one with clinical features of completed induction and were transitioned to daily oral azathioprine (2-3 ERA, the other with clinical features of FM. Most often with the initial phone mg/kg/day). Three patients were switched from azathioprine to mycopheny- call the RC date was provided and recorded, but not accepted (immediate late mofetil due to intolerance or increased disease activity. At last follow-up, responders). Some respondents asked for and received additional patient based on the PSOM and clinical assessment, 12 out of the 16 patients who information prior to providing a RC date (delayed responders). For this study received therapy by protocol had complete neurological recovery. Two WT was defined as the time from acquisition of a RC date to the actual patients had mild deficits including visual and cognitive symptoms. Two appointment date. WT for ERA and FM were calculated by province and by patients had moderate deficits including visual, motor, and cognitive symp- city (>500,000 population). toms. No patients had severe deficits. Results The response rate of 303 adult rheumatologists was 84% for ERA and Conclusion Immunosuppressive therapy of small vessel cPACNS was asso- 90% for FM. Of responders, 185/254 for ERA provided a median WT of 58 ciated with complete neurological recovery in 75% of patients. We propose a days (range 2-912), compared to 188/274 for FM providing a median WT treatment protocol for this patient group consisting of 7 pulses of IV of 105 days (range 2-1,460). Responders not providing a RC appointment cyclophosphamide over 6 months, and a weaning course of oral prednisone date were categorized by reason. Among cities there was no correlation over 9 months, followed by maintenance therapy of azathioprine or between WT and the population to rheumatologist ratio. The median RC- mycophenylate mofetil. WT for those who provided a date on initial contact (immediate responders) was not significantly different from those who asked for more information 39 before providing an appointment date, (delayed responders). For the 154 Consistent Inhibition of Structural Damage Progression by Rituximab in rheumatologists providing RC appointments for both mock patients in 107 Medically Important Subgroups of Patients with an Inadequate the WT was shorter for the mock ERA patient. In 7 the WT was identical, Response to TNF Inhibitors: Week 56 REFLEX Results and in 40 the WT was less for the mock FM patient than for the mock ERA Stanley Cohen (Radiant Research, Dallas, TX), Vivian Bykerk (Mount Sinai patient. Hospital, University of Toronto), Maxime Dougados (Hopital Cochin, Paris, Conclusion The median WT for RC in Canada is 58 days for patients with France), Mark Genovese (Stanford, Palo Alto, CA), Gerd Burmester (Charité ERA and 105 days for patients with FM. The median WT for RC shows a – University of Medicine Berlin, Berlin, Germany), Maria Greenwald (Desert wide variation across provinces and cities. No significant difference was Medical Advances, Palm Desert, CA), Tore Kvien (Diakonhjemmet Hospital, noted in the WT between rheumatologists who provided an RC date at first Oslo, Norway), M Cravets (Biogen Idec, Inc., San Diego, CA), Tim Shaw contact, compared to those responding later. There is a need to better manage (Roche Products Ltd, Welwyn Garden City, United Kingdom), D Hagerty RC waiting lists to shorten the WT for ERA patients (Biogen Idec, Inc., San Diego, CA) Disclosures No conflict of interest to declare. Peer reviewed funding pro- Objective To understand whether rituximab (RTX) was broadly effective vided by “The Canadian Initiative for Outcomes in Rheumatoid Arthritis”. upon structural damage progression in RA patient (pt) subgroups. Protocol approved by the Research Review Board Inc. Methods Pts receiving MTX and with an inadequate response to TNF

Downloaded on September 27, 2021 from www.jrheum.org inhibitors were randomized to RTX or placebo (PLA) (Cohen, A&R, 41 2006;54:2793-2806). Radiographs of hands and feet were obtained at base- Antineutrophil Cytoplasmic Antibodies in Systemic Lupus line (BL), Wk 24 and Wk 56. Pts were analyzed according to their original Erythematosus: Significance of Antibody-specific ANCA Measurement treatment group assignment. Scoring used the Genant-Sharp method. The pri- in SLE mary analysis population was comprised of pts at BL and 1 on-study radi- Desiree Tulloch-Reid (University of Toronto), Dafna Gladman (University of ograph. For pts missing the Wk 56 film, the Wk 24 score was linearly extrap- Toronto), Dominique Ibanez (University of Toronto), Murray Urowitz olated to Wk 56. The following subgroups were analyzed by BL status: sex, (University of Toronto) RF +/-, anti-CCP2 +/- and region [US vs non-US]. BL disease duration (DD), Objective To determine whether antibody-specific antinuclear cytoplasmic DAS28, C-reactive protein (CRP), and Total Sharp score (TSS) were analyzed antibodies (ANCA) against myeloperoxidase (MPO) and proteinase 3 (PR3) by quartiles (Q). could serve as a useful biomarker for lupus activity or specific patterns of Results The intent-to-treat population consisted of 201 PLA and 298 RTX- organ involvement in systemic lupus erythematosus (SLE). treated pts. The primary analysis population consisted of 184 (92%) PLA vs. Methods Patients with SLE followed prospectively in a single centre were 273 (92%) RTX-treated pts. RTX significantly inhibited structural damage included. Patients are followed at 2-6 month intervals according to a standard measured by the mean change in Sharp-Genant Total Score from BL to Wk protocol which includes complete history, physical examination and laborato- 56 (p=0.0046). The mean change from BL in RTX-treated pts was 1.00 vs. ry evaluation. All items necessary to complete the SLE Disease Activity Index 2.31 in pts who received PLA. Similar and consistent results were observed 2000 (SLEDAI-2K) are measured prospectively, and features of vasculitis, for nearly all subgroups analyzed. For RTX-treated pts vs PLA, ≥50% inhibi- renal, CNS involvement are documented. Since 1995 ANCA has been meas- tion of structural damage progression was observed for RF+ (0.98 vs 2.07) ured by ELISA on a once yearly basis. Patients attending the clinic from 2000 and RF- (1.10 vs 3.30) pts, males (1.31 vs 4.35) and females (0.93 vs 1.80), onward were reviewed in the study. Frequency of positive ANCA, defined by US (0.74 vs 1.76) and non-US (1.35 vs 3.01) pts, and for most quartiles of BL the standard reference range (≥ 180 AAU/ml), was assessed and correlated DD, DAS28, CRP, TSS, HAQ and DD (Table). An exception was BL anti- with SLEDAI-2K and features of renal disase, CNS activity and vasculitis, CCP2 where >50% inhibition of progression was observed for anti-CCP2+ using X2 analysis and Fisher’s exact test. pts (0.85 vs 2.21) but not for anti-CCP2- pts (0.97 vs 1.09). However, the Results ANCA was measured in 2755 visits in 758 patients with SLE. MPO- number of anti-CCP2- pts was small (33 RTX vs 21 PLA). and PR-3 ANCA were found in only 72 (9.5%) patients and 96 (3.5%) of vis- Conclusion RTX significantly inhibited structural damage progression at its, primarily against MPO. No correlation was found between the presence of week 56 in pts with an inadequate response to TNF inhibitors. RTX also con- MPO- or PR3- ANCA and lupus activity as defined by SLEDAI-2K sistently inhibited structural damage progression in clinically important sub- (SLEDAI-2K of 4.97 in the presence of ANCA and 4.77 in its absence, groups. These results support the broad inhibition of structural damage pro- p=0.71). There was a trend toward higher frequency of MPO-ANCA in the gression in this refractory population of RA pts. presence of documented vasculitis, but this failed to reach statistical significance (6.2% with vasculitis vs 3.1% without, p=0.11). No correlation existed 40 between the presence of MPO- or PR3-ANCA and disease manifestations of An Evaluation of the Influence of Temporal Artery Biopsy Result on renal or CNS disease. Similarly, no such associations were found for the13 Subsequent Corticosteroid Use patients having very high ANCA levels of >500 AAU/ml. Randy Walker (University of Saskatchewan, Department of Ophthalmology), Conclusion MPO- and PR3-ANCA are an infrequent and nonspecific finding Riley Hall (University of Saskatchewan, College of Medicine), Robert in systemic lupus erythematosus. Pekush (University of Saskatchewan, Department of Ophthalmology), Regina Taylor-Gjevre (University of Saskatchewan, Department of 42 Rheumatology) Effectiveness of Adalimumab (Humira) in Clinical Practice: Results from Objective The purpose of this study was to evaluate a subset of patients who the ACCLAIM Study in Patients with Psoriatic Arthritis underwent temporal artery biopsies (TABs) and how this biopsy determined DD Gladman (University of Toronto), RL Wong (Abbott Laboratories), B subsequent corticosteroid use secondary to a diagnosis of giant cell arteritis Guerette (Abbott Laboratories) (GCA). Objective To evaluate the effectiveness and safety of adalimumab in patients Methods A retrospective chart review of patients who received TABs between with active psoriatic arthritis (PsA) and a history of inadequate response to January 1995 and March 2005 for a suspected diagnosis of GCA was under- prior therapies. taken. Data was extracted from the charts and included clinical presentation, Methods ACCLAIM was an open-label, multi-center, Phase IIIb study con- biopsy result, duration and dosage of steroid therapy, whether or not the ducted in Canada. Patients with active PsA and insufficient response to prior patient received osteoporosis prevention, and clinical course descriptors. disease-modifying antirheumatic therapies (including methotrexate, and, for Results 130 TABs were performed on 115 patients. Of these, 23 of the biop- some patients, biologic therapies) received adalimumab 40 mg subcutaneous- sies (17.7%) were reported as positive. 15 patients had a repeated biopsy and ly every other week for 12 weeks. Effectiveness evaluations at Week 12 3 of these were reported as positive (20.0%). 29 patients were given a diag- included measurements for active dactylitis and enthesitis, as well as nosis of GCA. Corticosteroid therapy was commenced pre-biopsy in 89 of the ACR20/50/70 and Psoriasis Area and Severity Index (PASI) 50/75 response 115 patients (77.3%) but continued in only 6 patients without positive biop- rates. Physical function was assessed using the disability index of the Health sies. Of these patients, one had a strong clinical suspicion of GCA, but no Assessment Questionnaire (HAQ DI). Safety assessments included collection artery was isolated in the biopsy, two had ‘indeterminant’ biopsy results and of adverse events (AEs), and serious AEs. a history of PMR, and three had negative biopsy reports. Of the three with Results A total of 127 patients were enrolled at 35 sites. Baseline character- negative biopsy reports, one was felt to have “healed arteritis” as a result of istics were: mean age=49 years; % male=54; mean psoriasis duration=21 long-term prednisone therapy and another had a history of PMR. The average years; mean psoriatic arthritis duration=11 years; % with prior exposure to duration of corticosteroid therapy was 47.4 weeks (standard deviation = 25.8 biologic therapies=29.1%. The percentage of patients with active dactylitis weeks) with a range of 16 weeks to 118 weeks. decreased from 47% at baseline to 24% at 12 weeks (p<0.001). Similarly, the Conclusion In our facility, the temporal artery biopsy was virtually the sole percentages of patients with plantar fascia enthesitis and Achilles tendon determinant of whether or not a patient was treated for temporal arteritis. A enthesitis decreased from 24% and 30% at baseline, respectively, to 11% and second temporal artery biopsy was only attempted in those who had a very 14%, respectively, at 12 weeks (p<0.008 vs. baseline). At Week 12, convincing clinical picture of GCA and even in these patients, if the biopsy ACR20/50/70 response rates were 74%, 51% and 32%, and PASI 50/75 was negative, the patient was diagnosed as GCA negative unless there was a response rates were 65% and 47%. There was a mean reduction in HAQ DI history of PMR or a suspicion of “healed arteritis”. of 0.44 (p<0.001). The ACR20/50/70 response rates were numerically greater

Downloaded on September 27, 2021 from www.jrheum.org for patients who were naïve to biologics vs. those who were not (81%, 60% changes over the distal portion of the affected digit. Allen’s test was grossly and 26% vs. 70%, 46% and 11%, respectively; p>0.05), as was also the case abnormal bilaterally. No other abnormalities were perceived on physical for the improvements in PASI 50/75 (78% and 56% vs. 46% and 35%; examination, specifically, no vascular bruits, sclerodactyly, or respiratory p=0.007 for between-group PASI 50 comparison). Upper respiratory tract abnormalities were noted. Angiography revealed diffuse distal vasculopathy infection (4.7%) and headache (4.7%) were the only AEs reported in >4% of in both upper extremities. Laboratory examination revealed a positive ANA patients. Three SAEs were reported, but none were considered related to adal- > 1280 with centromere specificity. Anti-ds DNA Ab, ENA Ab, Anti-cardi- imumab therapy. No cases of serious infection, malignancy, tuberculosis, con- olipin Ab were all negative. Echocardiogram, Pulmonary Function testing gestive heart failure, or demyelinating disease were reported. parameters were within normal limits. An upper gastrointestinal examination Conclusion Adalimumab-treated patients achieved significant improvements did not reveal any esophageal dysmotility, A high resolution CT chest did not in both the skin and joint manifestations of psoriatic arthritis, as well as in reveal any abnormality. physical function. Adalimumab was generally well-tolerated. These results, An obliterative vasculopathy has been reported in occasional cases in the obtained from routine clinical practice, are consistent with results from other presence of anti-centromere antibodies. This has generally been in the setting trials of adalimumab in the treatment of psoriatic arthritis. of a pre-existing diagnosis of systemic sclerosis. Conclusion Anticentromere antibodies may be a marker for digital vascu- 43 lopathy in patients with and without other evidence of systemic sclerosis. Sociodemographic and Clinical Correlates of Fatigue in Patients with Systemic Sclerosis: Evidence from 482 Canadian Scleroderma Research 45 Group Registry Patients Targeted Inhibition of the IL-6 Receptor with Tocilizumab Effectively Brett Thombs (McGill University), Marielle Bassel (McGill University), Reduces Disease Activity in Patients with Rheumatoid Arthritis Marie Hudson (McGill University), Suzanne Taillefer (McGill University), Andre D Beaulieu (Université Laval), Michel Zummer (CH Maisonneuve- Murray Baron (McGill University), Rosemont), Andrea Rubbert-Roth (University of Cologne), Thasia Woodworth Objective To identify demographic, socioeconomic, and disease, correlates (Roche Products Ltd), Emma Alecock (Roche Products Ltd), Rieke Alten of fatigue in a pan-Canadian cohort of patients with systemic sclerosis (SSc). (University Medicine Berlin), Josef Smolen (Medical University of Vienna) Methods 482 patients enrolled in the Canadian Scleroderma Research Group Objective An emerging therapeutic approach for RA treatment is targeted (CSRG) Registry between September 2004 and August 2007. Fatigue was inhibition of IL-6 signaling. The aim of this study was to test the efficacy and measured using the Vitality subscale of the SF-36. Kendall’s tau correlations safety of tocilizumab (TCZ), a novel humanized anti-human IL-6 receptor were used to assess the bivariate association between sociodemographic, antibody, in patients with moderate to severe active RA despite treatment with medical, and psychosocial variables with fatigue. Multivariable associations methotrexate (MTX). between demographic (step 1), socioeconomic (step 2), global disease (step Methods 623 patients were evaluated in this randomized, double blind, place- 3), and specific disease factors (step 4) with the SF-36 Vitality Scale were bo controlled phase 3 trial. Patients received either 8 mg/kg TCZ, 4 mg/kg assessed using hierarchical multiple linear regression. The association TCZ, or placebo intravenously every 4 weeks. All groups received MTX at between symptoms of depression and pain with fatigue were analyzed in a stable pre-study doses (10-25 mg weekly) throughout the study. No other dis- separate regression equation from disease factors, also controlling for ease-modifying anti-rheumatic drugs (DMARDs) were allowed. sociodemographic variables. Results A significantly higher proportion of TCZ-treated patients showed Results Demographic variables (gender, age) accounted for 0.04% of the improvements in the primary endpoint, ACR20 at 24 weeks (TCZ 8 mg/kg variance, and socioeconomic variables (marital status, education) accounted 59%; TCZ 4 mg/kg 48%; placebo 27%; p<0.0001). Significantly more for another 0.03% of the variance. Global disease and severity factors (dura- patients also achieved ACR50 and ACR70 response by 24 weeks with TCZ 8 tion, physician global) accounted for an additional 5.8% of the variance. mg/kg and TCZ 4 mg/kg vs. placebo (ACR50: 44% and 32% vs. 11%, respec- Specific disease factors accounted for an additional 23.3% of the variance in tively; ACR70: 22% and 12% vs. 2%, respectively, p <0.0001). A total of 21 Step 4. Of the specific disease factors, diffuse status (ß=0.09, p < .028), patients achieved ACR90 response, 11 (5.4%) with TCZ 8 mg/kg and 10 breathing problems (ß=0.23, p < .001), number of gastrointestinal symptoms (4.7%) with TCZ 4 mg/kg vs. none for placebo. Significant improvements in (ß=0.28, p < .001) and comorbid health problems (ß=0.11, p < .010) were sig- all ACR core set parameters were observed with TCZ 8 mg/kg and 4 mg/kg vs. nificant predictors. In addition, in a subsequent analysis of psychosocial cor- placebo, with highly significant differences (p <0.0001) for many components relates, depression (ß=0.48, p < .001) and pain (ß=0.29, p <.001) were inde- (TJC, SJC, ESR with TCZ 4 mg/kg; TJC, SJC, patient’s global assessment of pendently associated with fatigue even after controlling for demographic and disease activity, patient’s assessment of pain, ESR and CRP with TCZ 8 socioeconomic variables. mg/kg). CRP levels dropped to normal at 2 weeks’ treatment with 8 mg/kg Conclusion SSc disease-related factors and symptoms (e.g., pain, depres- TCZ and remained normal to study end. A similar overall frequency of adverse sion), but not sociodemographic variables, significantly predicted fatigue in events (AEs) was reported in all groups. Of 41 serious AEs (approximately 6% multivariable analysis. In other chronic disease groups fatigue is treated with of patients in each group), 15 were considered related to study treatment and medication, exercise and self- management strategies. Similar interventions 11 led to drug discontinuation. Serious infections were observed with a higher should target fatigue or the factors that likely cause fatigue in SSc. frequency in patients treated with TCZ (2.9% in the TCZ 8 mg/kg group, 1.4% in the TCZ 4 mg/kg group and 1% in the placebo group). 44 Conclusion This large phase 3 study provides evidence that IL-6 plays a fun- Digital Gangrene in a Patient with Anti-Centromere Antibodies But No damental role in maintaining the inflammation that drives RA. Inhibition of Other Stigmata of Systemic Sclerosis the IL-6 receptor and the subsequent signaling cascade with TCZ improves Lauren Bolster (University of Saskatchewan), Regina Taylor Gjevre the signs and symptoms of RA significantly, with a good safety and tolerabil- (University of Saskatchewan) ity profile. Objective We report a case of digital gangrene associated with an obliterative vasculopathy and anticentromere antibodies in a patient with no pre-existing 46 stigmata of systemic sclerosis. Sustainability of Anti-TNF Therapy in Spondyloarthropathies in Results We report a 53 year old woman with a past medical history of Wolfe Standard Practice Parkinson White syndrome treated with verapamil,dating back to childhood Nathalie Morency (University of Montreal), Elham Rahme (McGill who presented with progressive pain and blackening of the distal right third University), Boulos Haraoui (Hopital Notre-Dame, Centre hospitalier uni- finger over the preceding 5 weeks. She denied any pre-existing Raynauds versitaire de Montreal (CHUM)), Eric Rich (Hopital Notre-Dame, CHUM), syndrome. She is a never-smoker. Examination revealed obvious gangrenous Yves Troyanov (Hopital Notre-Dame, CHUM), Jean-Pierre Raynauld

Downloaded on September 27, 2021 from www.jrheum.org (Hopital Notre-Dame, CHUM), Carol Anne Yeadon (Hopital Notre-Dame, PBO) had transient elevation > 3xULN, with only 1 patient withdrawing. CHUM ), Jean-Pierre Pelletier (Hopital Notre-Dame, CHUM), Anne St- Elevated total cholesterol was observed in TCZ: 22.9%/PBO: 5.6%, with Pierre (Hopital Saint-Luc, CHUM), Jean-Luc Senecal (Hopital Notre-Dame, increased LDL in 16.1%/3.4% of patients, respectively. Improvement in HDL CHUM), Bernard Bissonnette (Hopital Sacre-Coeur), Francois Beaudet was observed in TCZ: 15.0%/PBO: 6.0% of patients. The ApoB/ApoA (Hopital Sacre-Coeur), Denis Choquette (Hopital Notre-Dame, CHUM) atherogenic index was unchanged. Serious AEs were reported in TCZ: 6.7% Objective To determine the sustainability of anti-TNF (tumour necrosis fac- and PBO: 4.3% of patients, with serious infections reported in 2.7% vs. 1.9% tor) in patients with spondyloarthropathies (SpA) in a daily rheumatology of patients. AE leading to withdrawal were low in both groups (TCZ: practice, and identify the reasons for stopping or switching to another anti- 3.9%/PBO: 1.9%). TNF agent. Conclusion The study confirms that TCZ is highly effective in reducing artic- Methods Charts of all patients with SpA ever treated with an anti-TNF agent ular and systemic symptoms and has a favorable risk/benefit profile when for axial involvement in three different practices were reviewed. Eligible combined with background DMARDs. patients had a confirmed diagnosis of SpA made by a rheumatologist and had evidence of axial involvement justifying initiation of an anti-TNF therapy. 48 Disease duration, past treatment, baseline and follow up BASDAI, BASFI, Access to Anti-TNF Therapy for Rheumatic Diseases: A Public/ Private physical metrology, CRP, ESR, side effects and reason for discontinuation Discrepancy and switches were collected. Lesley Bautista (Memorial University of Newfoundland), Yatish Setty Results 86 patients fulfilled the selection criteria for this study. 51 patients (Memorial University of Newfoundland), Rose Ardern (Memorial University were initially treated with infliximab (59%), 21 with etanercept (24%) and 14 of Newfoundland), Proton Rahman (Memorial University of Newfoundland) with adalimumab (16%). The respective sustainability of theses drugs at 6 Objective We set out to examine the demographic and disease related char- months was 92%, 95% and 100%. Most patients switched to an alternate anti- acteristics in RA and PsA patients accessing anti-TNF therapies through pub- TNF and only three patients discontinued all biologic therapy : one for sur- lic plans as compared to private insurance plans. gery and sinusitis, one for herpes zoster and cellulitis, and the last one due to Methods Charts of patients starting anti-TNF therapy were systemically lack of efficacy. 25 switches occurred and 5 patients switched to a third or reviewed with a standardized protocol from two rheumatology clinics at went back to their first anti-TNF. In 15 patients, side effects were the cause Eastern Health in St. John’s, NL. In total, 58 RA patients and 49 PsA patients for switching to another agent (50%) and loss or lack of efficacy in 12 (40%). were identified. Conclusion Compare to previous published data, our result shows different Results With respect to RA, 22 patients (38%), were covered by government survival on therapy at 6 months. Reasons for these differences are explored. or other compassionate drug programs (public plans) and 36 patients (62%), had private insurance. Patients acquiring anti-TNF agents through public 47 plans as compared to private insurance were exposed to a greater number of IL-6 Receptor Inhibition with Tocilizumab Reduces Disease Activity in DMARDS prior to initiation of anti-TNF therapy: median 3 (range 2 to 6) vs Patients with Rheumatoid Arthritis with Inadequate Response to a median 2 (range 1 to 4); had a greater disease duration 14.5 years (sd 11.2) vs Range of DMARDs: The TOWARD Study 6.6 years (sd 7.7); p=0.01 and a greater number of active joints 17.7 (sd 8.1) M Genovese (Stanford University School of Medecine, Stanford, CA, USA), vs 9.9 (sd 5.7); p = 0.0003. J P Brown (Laval University, Quebec, Canda), J McKay (Oklahoma State With respect to PsA patients, 8 were covered through public plans and 41 University, Tulsa OK, USA), E Nasonov (Institute of Rheumatology, patients had private insurance. Patients acquiring anti-TNF agents through Moscow, Russian Federation), E Mysler (Organization fro Medical public plans as compared to private insurance were exposed to a greater num- Investigations, Buenos Aires, Argentina), N da Silva (Federal University of ber of DMARDS prior to initiation of anti-TNF therapy: median 2 (range 2 to Goiàs, Goiania, Brazil), E Alecock (Roche Products Ltd, Welwyn, UK), J 4) vs median 1 (range 1 to 3); had a greater disease duration 18.8 years (sd Gomez-Reino (University of Santiago de Compostela, Santiago de 16.0) vs 10.4 years (sd 8.1); p= 0.17 and a greater number of active joints 12.8 Compostela, Spain) (sd 8.6) vs 6.1 (sd 4.7); p = 0.06. The lack of statistical difference in the PsA Objective Interleukin-6 (IL-6) plays a key role in rheumatoid arthritis (RA). patients is likely due to the small number of patients receiving anti-TNF ther- Inhibition of IL-6 signaling is a novel approach to the treatment of RA. This is apies (8) from public plans. the largest study in the US and Europe examining the efficacy and safety of Conclusion Patients with inflammatory arthritis initiating anti-TNF therapies tocilizumab (TCZ), a humanized anti-IL-6 receptor antibody, in patients with on public plans were on greater number of DMARDs, had greater disease moderate to severe active RA with inadequate response to a range of DMARDs. duration and active joints as compared to those with private plans. Methods TOWARD was a 24 week phase III, randomized (2:1), placebo-controlled study. Patients (N=1216) had active RA despite treatment with one or 49 more traditional DMARDs. Patients continued stable doses of DMARDs and Extended Follow-up of the Long-term Safety of Rituximab in received TCZ 8 mg/kg or placebo (PBO) intravenously, every 4 weeks for 24 Rheumatoid Arthritis weeks. Efficacy results are presented as an ITT analysis. Ronald van Vollenhoven (Karolinska University Hospital), Boulos Haraoui Results Mean baseline characteristics were similar between treatments (Université de Montréal), Paul Emery (Leeds General Infirmary), Clifton (TCZ/PBO): RA duration: 9.8/9.8 years, DAS28: 6.7/6.6, TJC: 30.1/29.1, Bingham (Johns Hopkins Univeristy), Edward Keystone (University of SJC: 19.7/18.7, HAQ: 1.5/1.5, CRP: 2.6/2.6 mg/dL. At week 24, Toronto), Maria Greenwald (Desert Medical Advances), Larry Moreland ACR20/50/70 responses were significantly higher in the TCZ group vs. PBO (University of Alabama), Marianne Sweetser (Biogen Idec), Karen Rowe (60.8% vs 24.5%, 37.6% vs. 9.0%, and 20.5% vs. 2.9%, respectively) and (Roche Products Ltd), Bridget Wagner (Genentech Inc), Fabio Magrini there was a measurably higher ACR20 response rate in the TCZ arm already (Roche Products Ltd) apparent at week 2. Patients in the TCZ group with DAS28 <2.6 was 30.2% Objective To provide an update on the long-term safety evaluation of ritux- compared to 3.4% receiving PBO with a mean change in DAS28 in both imab (RTX) in patients (pts) with active rheumatoid arthritis (RA). groups of -3.17 and -1.16, respectively. CRP and hemoglobin levels improved Methods Safety analyses were performed on 1053 RA pts exposed to RTX as after week 2 in the TCZ arm and tended to normalize by week 24. The inci- of September 15, 2006 in the clinical trial program. Data on pts receiving up dence of adverse events (AEs) was 72.8%/61.1% in TCZ/PBO groups. The to 4 treatment courses are reported. most frequent AEs (TCZ/PBO) were URTI (8.4%/6.8%), nasopharyngitis Results Data represent 2438 pt-years [yrs] of exposure; pts received up to 7 (5.9%/4.8%), headache (5.0%/3.9%) and hypertension (5.0%/2.7%). treatment courses. A total of 684, 400 and 142 pts received ≥2, ≥3 and ≥4 Infection rate was 1.2/0.95 per 100 patient years. Of the 8% of patients with courses of RTX, respectively. Incidence of adverse events (AEs) decreased elevated baseline ALT in each group, 1% of patients in TCZ group (none in from 88% (931/1053) of RTX pts after Course 1 (C1) to 81%, 72%, and 65%

Downloaded on September 27, 2021 from www.jrheum.org after C2, C3, and C4, respectively. Serious AEs (SAEs) followed a similar good response of skin scores to methotrexate (MTX), with significant wors- pattern, decreasing from 18% after C1 to 15%, 10%, and 3% after C2, C3, and ening after stopping MTX and subsequent improvement after restarting MTX. C4, respectively. Acute infusion reactions (first infusion, each course) This provides indirect evidence for the efficacy of MTX in dSSc. decreased from 23% (C1) to 11% (C4) and from 7% (C1) to 2% (C2) (second Methods The SSc database of patients seen in a tertiary referral clinic from infusion, each course). A total of 702 pts (67%) experienced ≥1 infection. The January to July 2007 was searched for dSSc patients who had been on MTX most common infections were upper respiratory tract infections (32%) and with good response and progression after MTX was stopped. The disease urinary tract infections (11%). Serious infections per 100 pt-years were 5.36 characteristics and clinical course of these patients are described. The modi- after C1 (confidence interval, 4.26-6.74), followed by 4.6 (CI, 3.27-6.47), fied Rodnan skin score (mRSS) was compared over 3 time periods: 1. First 6.34 (CI, 3.94-10.20), 5.41 (CI, 2.03-14.41) after C2, C3, and C4, respective- MTX treatment period 2. Interval when MTX treatment was stopped 3. ly. The proportion of pts with IgM and IgG levels below the lower limit of Second MTX treatment period to last clinic evaluation. The change in mRSS normal increased with further treatment courses. No opportunistic infections, and the rate of mRSS change were calculated for each time period using the viral reactivations or tuberculosis were reported. A total of 36 malignancies peak or trough mRSS within 6 months of starting or stopping MTX. A clini- (18 in C1, 13 in C2, 4 in C3, and 1 in C4) occurred in 32 pts (3%). No lym- cally significant change in mRSS is defined as ≥ 30% of baseline or rate of phoproliferative malignancies and no increased risk of malignancy with addi- change ≥ 5 units/year. tional courses of treatment were observed. Results Of 167 charts reviewed, 47 SSc patients had been on MTX. Three Conclusion This further update on the long-term follow-up (2438 pt-yrs) of dSSc patients (2 females, 1 male) fulfilling ACR classification criteria had RA pts receiving RTX showed a safety profile consistent with that reported good response of their mRSS to MTX and progression when MTX was previously. After 4 courses, a slight upward trend was observed in the rate of stopped. Previous medications included cyclosporine and penicillamine. Age infections; however, the rate of serious infections remained stable with repeat- at disease onset was 39 to 51 years. One was positive for anti-Scl-70, and 2 ed treatment. were positive for ANA (speckled & nucleolar), without detectable antibodies against Scl-70 or centromere. All patients had Raynaud’s phenomenon, joint 50 and gastrointestinal involvement. Patient 2 had a watermelon stomach and Evaluation of the SF-12 in Early Inflammatory Arthritis (EIA) Barrett’s esophagus. Patient 3 had mild pulmonary fibrosis. None had pul- Carly K. Cheng (Rheumatology, Mount Sinai Hospital), Vivian P. Bykerk monary hypertension or renal crisis. MTX was started between 0.5 to 4 years (Rheumatology, Mount Sinai Hospital), Ludmila Mironyuk (Rheumatology, of disease onset. All patients had > 30% mRSS improvement and were on Mount Sinai Hospital) MTX for 1.9 to 5.8 years (period 1). In patients 2 and 3, MTX was stopped Objective The purpose of this analysis is to determine how closely the SF-12 for about 6 months before mRSS progressed from 20 to 32 & 13 to 29 respec- and SF-36 physical and mental component summaries correlate in patients tively. In patient 1, MTX was stopped for 2 years before mRSS progressed with early inflammatory arthritis in order to determine if the shorter 12 item from 6 to 17 after nearly 9 years of disease. All patients responded to reintro- questionnaire is interchangeable in this patient group. duction of MTX. Methods Clinical cohorts collect patient derived outcomes in the form of Conclusion The above cases provide indirect evidence for the efficacy of questionnaires measuring disease activity, quality of life and function in order MTX in the treatment of dSSc. to measure change over time. In order to prevent patient “questionnaire completion fatigue”, it is important to limit questions asked at each assessment. 52 The 36-Item Short-Form Health Survey (SF-36) is a 36 question health-relat- Disease Activity in a Cohort of RA Patients Treated with Anti-TNF ed measure of quality of life. The 12-Item Short-Form Survey (SF-12) is a Agents, and Followed at an Academic Center subset of the SF-36 which has been validated in other settings, but has yet to Elena Ciubotariu (Université de Montréal), Boulos Haraoui (Université de be validated in early inflammatory arthritis (EIA). The Toronto Early Arthritis Montréal) CoHort (TEACH) is a prospective observational «real world» cohort of Objective To evaluate the clinical status of a cohort of RA patients treated patients with EIA who complete the SF-36 at baseline and annually during fol- with a stable regimen of anti-TNF therapy. low-up. We present an analysis from the first 94 patients with EIA who were Methods A cohort of unselected patients with active RA treated for a mini- recruited to TEACH according to the following criteria: >16 years old, symp- mum of 3 months with an anti-TNF drug were evaluated during 2 consecutive toms for >6 weeks and < 12 months, and 2 or more swollen joints or 1 swollen visits at 3 month interval. Demographic (age, sex, disease interval, presence MCP or PIP and 1 of: positive RF, anti-CCP,AM stiffness > 45 min, a response of erosions and RF) and clinical data (past and actual treatment received, type to NSAID or painful MTP squeeze test, no evidence of another connective tis- of TNF-α inhibitor used) were obtained from patients charts. At the first and sue disease, likely to be RA. Patients were usually treated with initial DMARD the 3-month, the following clinical outcomes and their components were col- therapy more often consisting of combination MTX + HCQ ±SSZ. Patients are lected: HAQ (Health Assessment Questionnaire), DAS28, SDAI (Simplified followed prospectively according to a standardized protocol. Patients were Disease Activity Index) and CDAI (Clinical Disease Activity Index). assessed every 3 months and if necessary, therapy was adjusted targeting for Results A total of 100 consecutive patients (mean age 54 years) with long remission (remission=zero swollen joints). SF-12 scores were compared to the standing disease (mean duration 13 years), 23 on Adalimumab, 19 on SF-36 scores using Pearson correlation coefficients. Infliximab and 58 on Etanercept, were included in this analysis. At the base- Results The physical component summary has a correlation coefficient of line visit the mean HAQ was 0.71 and the DAS28 was at 3.33 with an SDAI 0.918 (p<0.01). The mental component summary has a correlation coefficient of 19 and a CDAI at 12. All parameters of disease activity remained stable at of 0.955 (p<0.01). Further analyses will be conducted to determine whether 3 months with DAS28 score of 3.1 and a HAQ score 0.66. At the 3 months or not this relationship holds true over time. evaluation, 36% of patients were in low disease activity and 21% achieved a Conclusion The SF-12 appears to be a valid instrument as a measure of state of remission based on DAS 28. There were no overall differences in quality of life for use in patients with early inflammatory arthritis. The SF-12 response rates and disease control between the three anti-TNF therapies. The is highly correlated with the SF-36 at baseline. The results from this study SDAI and CDAI scores correlated well with the DAS28 and HAQ at baseline suggest that it is sufficient to collect the SF-12 in patients with early arthritis. and control Conclusion The clinical response in this cohort of patients with severe, long- 51 standing RA treated with TNF-α inhibitors is comparable to those achieved in Indirect Evidence for the Efficacy of Methotrexate in Diffuse Systemic controlled clinical trials and long term observational databases. The SDAI and Sclerosis CDAI represent valid and easy to perform assessments of disease activity and Andrea Hsiu Ling Low (Mt Sinai Hospital), Peter Lee (Mt Sinai Hospital) treatment response comparable to the DAS28, and could be easily incorpo- Objective We report 3 diffuse systemic sclerosis (dSSc) patients who had rated in daily clinical practice.

Downloaded on September 27, 2021 from www.jrheum.org 53 Results All BZA doses and RLX prevented bone loss, whereas PBO was Type 1 DM and Psoriatic Arthritis associated with significant reductions in BMD. The difference in percent Natasha Pardy (Memorial University of Newfoundland), Mohammed Uddin change of lumbar spine BMD from baseline to 24 months relative to PBO was (Memorial University of Newfoundland), Kajree Islam (Memorial University 1.08%, 1.41%, 1.49%, and 1.49% for 10 mg, 20 mg, 40 mg BZA and 60 mg of Newfoundland), Lesley Bautista (Memorial University of Newfoundland), RLX, respectively (P <0.001 for all comparisons). Comparable BMD Sean Hamilton (Memorial University of Newfoundland), Yatish Setty responses were observed with BZA at other skeletal sites. Significant (Memorial University of Newfoundland), Rose Ardern (Memorial University decreases in serum osteocalcin and C-telopeptide levels from baseline and rel- of Newfoundland), Lynette Peddle (Memorial University of Newfoundland), ative to PBO were observed as early as 3 months and remained sustained Proton Rahman (Memorial University of Newfoundland) through study end (P <0.001). By Month 24, median serum osteocalcin lev- Objective Epidemiological studies note an increased incidence of psoriasis els decreased from baseline by 21%, 22%, 22%, and 27% with BZA 10, 20, and psoriatic arthritis (PsA), in subjects with type 1 diabetes mellitus (type and 40 mg, and RLX, respectively, and 6% with PBO (P <0.001 vs baseline 1 DM). Thus it is conceivable that there are common susceptibility genes for each); median serum C-telopeptide levels decreased by 25%, 24%, 22%, between PsA and type 1 DM. A recent genome wide scan reported associa- and 32% with respective BZA doses and RLX and 13% with PBO (P <0.001 tions with 11 robust candidates in type 1 DM. As a result we set out to exam- vs baseline for each). Overall, BZA was well tolerated and exhibited a favor- ine the association of these variants in a Caucasian PsA cohort. able safety profile. Methods All PsA patients had inflammatory arthritis in the presence of pso- Conclusion In conclusion, this study demonstrated that treatment with BZA, riasis. The PsA patients were Caucasians of North European descent. The a new SERM, prevented bone loss, reduced bone turnover, and was generally unrelated controls were of similar ethnicity to the PsA probands. We exam- well tolerated in postmenopausal women with normal or low BMD. ined 254 PsA probands and 243 controls. All samples were genotyped for a panel of 11 SNPs using the Sequenom MassARRAY system. 55 The SNPs genotyped were from susceptibility genes / regions including HLA Longitudinal Differences in RA Phenotype Between First Nations and class II (rs rs3129934); INS (rs rs689); PTPN22 (rs2476601); 12q24 (rs Caucasians rs3184504); 12q13 (rs2292239); 18p11 (rs1893217); 16 rs18932; 16p31 Christine Peschken (University Of Manitoba), Cheryl Barnabe (University (rs12708716); CTLA4 (rs3087243); CD25 (rs 1154656); IFIHI (rs1990760). Of Calgary), Carol Hitchon (University Of Manitoba), David Robinson Allele associations were calculated using the PLINK software. (University Of Manitoba), Hani El-Gabalawy (University Of Manitoba) Results All alleles genotyped satisfied the H-W equilibrium. Single markers Objective Native American Indians (NAI) have some of the highest docu- associations for the 11 SNPs identified two significant associations and anoth- mented prevalence rates of rheumatoid arthritis (RA) in the world, with little er association that demonstrated a trend. These associations were with 1) SNP available information on phenotype and comparative outcomes. This is the rs3184504 in 12q24 [OR 1.3 (95% CI 1.01 to 1.7); p=0.03]; 2) SNP rs first such description in a large cohort of NAI RA patients followed prospec- 1154656 in CD25 [OR 0.74 (95% CI 0.55 to 0.99); p=0.04] and 3) SNP tively and compared to a large cohort of Caucasian (C) RA patients followed rs2292239 in 12q13 [OR 1.25 (95% CI 0.96 to 1.63);p=0.09). These associa- at the same centre. tions were independent of type 1DM in patients with PsA. Methods The University of Manitoba Arthritis Centre (UMAC) maintains a Conclusion We detected a significant but modest association between CD25 prospective database on all patients seen since 1990. The UMAC database and PsA (also known as interleukin-2 receptor alpha chain) and a SNP in includes patients’ diagnoses, year of disease onset, date of first and subse- 12q24 locus. These associations are intriguing and require validation from quent visits to the Arthritis Centre, and self-reported ethnicity. At each visit, other groups. patients complete a modified health assessment score (mHAQ), pain, fatigue and global disease activity visual analogue scales (VAS), and physicians com- 54 plete a tender and swollen joint count, physician global VAS, current treat- Efficacy of Bazedoxifene for the Prevention of Postmenopausal ment information, serology and acute phase reactants, and update records of Osteoporosis: Results of a 2-Year, Phase III, Placebo- and Active- joint surgery. The database contains records of 7200 patients with rheumatic Controlled Study diseases as of May 30, 2007. Records of all patients with a diagnosis of RA D. L. Kendler (Osteoporosis Research Centre, Vancouver, Canada), P. D. who had self-identified as C or NAI were abstracted. Cumulative treatment Miller (University of Colorado Medical Center, Denver, CO, USA), C. data, ESR, mHAQ scores, VAS scores, and tender (TJC) and swollen joint Christiansen (Center for Clinical and Basic Research, Ballerup, Denmark), counts (SJC) over time and at last visit were compared. H. C. Hoeck (Center for Clinical and Basic Research, Ballerup, Denmark), J. Results Records of 1423 (323 NAI, 1100 C) RA patients were abstracted. D. Adachi (St. Joseph’s Hospital - McMaster University, Hamilton, Ontario, Mean disease duration was slightly longer in C compared to NAI (16±11 vs. Canada), E. M. Lewiecki (New Mexico Clinical Research & Osteoporosis 15±9 years, p=0.03). Average onset age was 33 years for NAI and 43 years Center, Inc, Albuquerque, NM, USA), G. Woodson (Atlanta Research Center, for C (p=0.001). NAI were more frequently positive for RF (86% vs. Decatur, GA, USA), M. Ciesielska (Wyeth Pharmaceuticals, Collegeville, 62%,p<0.001) and ANA (55% vs. 21%,p<0.001). Mean TJC and SJC were PA, USA), A. A. Chines (Wyeth Pharmaceuticals, Collegeville, PA, USA), not different, but NAI had significantly higher mean Lansbury scores (66.5 vs. G. Constantine (Wyeth Pharmaceuticals, Collegeville, PA, USA), P. D. 49.7, p<0.000), mHAQ scores (1.1 vs. 0.9, p=0.001), and ESR (31 vs. Delmas (University of Lyon and INSERM Research Unit 831, Lyon, France) 25mm/hr, p<0.012). VAS scores were also higher for NAI. Frequency of joint Objective Bazedoxifene (BZA) is a novel selective estrogen receptor modu- replacement surgery, prednisone use and biologic use was not different lator (SERM) currently in clinical development as monotherapy for preven- between the two groups, but NAI had a higher lifetime number of DMARDs tion and treatment of postmenopausal osteoporosis. In preclinical studies, (2.9±1.9 vs. 2.1±1.7, p<0.001), and were more frequently prescribed combi- BZA maintained skeletal mass without stimulation of the mammary gland or nation therapy (40% vs. 30%, p<0.001). endometrial tissue. This 2-year, Phase III study was designed to assess the Conclusion Compared to C, NAI RA patients are more frequently seropos- efficacy and safety of 3 BZA doses compared with placebo (PBO) and ralox- itive, and have greater large joint involvement, reflected by higher ifene (RLX) in the prevention of postmenopausal osteoporosis. Lansbury scores, and resulting in higher mHAQ scores, higher ESR, and Methods Healthy postmenopausal women (N = 1583; mean age: 57.6 y) with higher pain, fatigue and global VAS scores in spite of more aggressive lumbar spine or femoral neck BMD T-scores no less than -2.5 (mean, -1.2) DMARD treatment. were randomized to 1 of 5 groups: BZA 10, 20, or 40 mg, PBO, or RLX 60 mg. All women received 600 mg elemental calcium. The primary outcome 56 was percent change in lumbar spine BMD at 24 months; secondary outcomes Strategies to Reduce “Nuisance” Side Effects of Methotrexate: A included BMD at other skeletal sites and serum bone turnover markers. Systematic Review

Downloaded on September 27, 2021 from www.jrheum.org Gina Rohekar (University of Western Ontario), Janet Pope (University of and vitamin D (400 IU). The primary efficacy outcome was the incidence of Western Ontario) new vertebral fractures after 36 months; secondary outcomes included non- Objective To perform a systematic review of the evidence for any techniques vertebral fractures (NVFs). to reduce the non-serious, “nuisance” side effects of methotrexate (MTX), Results A total of 7492 subjects (mean age ± SD, 66.4 ± 6.7 years) were ran- except for folic acid or folinic acid. domized and received ≥1 dose of study medication. At baseline, mean LS T- Methods A systematic review was carried out in 3 databases using the OVID score was -2.4, mean total hip T-score was -1.4, and 56% of women had ≥1 interface: Medline, Embase, and the Cochrane Central Register of Controlled prevalent vertebral fracture (mostly mild). The 3-year incidences of new ver- Trials. Inclusion criteria included adults with rheumatoid arthritis being treat- tebral fractures, based on Kaplan-Meier estimates, were 2.3%, 2.5%, 2.3%, ed with MTX. Serious side effects were excluded, as well as the use of folic and 4.1% in the BZA 20 mg, BZA 40 mg, RLX 60 mg, and PBO groups, acid/folinic acid, other DMARDs, and NSAIDs. Results of the reviews of the respectively, with a relative risk reduction for new vertebral fracture of 42% databases were summarized with regards to relevance. (P = 0.015), 37% (P = 0.031), and 42% (P = 0.012), respectively, versus PBO. Results The Medline search found 947 articles, of which only 9 were relevant. There was overall no treatment effect on NVFs. In a post-hoc analysis of Likewise, the Embase search found 498 articles. Nine of these articles women with FN T-score ≤-3.0 or ≥1 moderate or multiple vertebral fracture were relevant, but only 3 had not been found in Medline. The Cochrane (n = 1772), NVF incidence was 4.9%, 6.5%, 8.4%, and 9.1% in the BZA 20 search detected 87 articles, of which 3 were relevant. All 3 articles were mg, BZA 40 mg, RLX 60 mg and PBO groups, respectively. Relative to PBO, found in Medline. Therefore, 13 articles in total were found, 4 of which BZA 20 mg reduced NVF incidence by 50% (P = 0.02). Similar reduction were randomized controlled trials. In most, the assessment of side effects was observed when both BZA doses were combined (40% reduction, P = was not the primary outcome of interest. Overall, the quality of the stud- 0.03). ies found was poor. Few directly addressed the issue of side effects as a Conclusion We conclude that BZA treatment significantly reduced the risk of primary outcome. new vertebral fractures, and in subjects at higher risk for fractures, was asso- Changing the route of administration from oral to parenteral was found to ciated with a significant reduction in NVFs. decrease gastrointestinal side effects. In a randomized trial of 212 patients total, 9% discontinued oral MTX but only 22% of these subsequently discon- 58 tinued intramuscular MTX. In a crossover study of patients forced to switch Is There Research Funding and Media Discrimination Against Arthritis? to oral MTX when the supply of intramuscular MTX ran out, 69 (48%) of Quincey Kirschner (Arthritis Consumer Experts), Meagan Hasek-Watt patients who tolerated intramuscular MTX could not tolerate taking it orally (Arthritis Consumer Experts), Cheryl Koehn (Arthritis Consumer Experts), due to nausea (p<0.001). As well, there was evidence that starting with a Dr. John Esdaile (Arthritis Research Centre of Canada), Dr. Kam Shojania lower dose of MTX (15 mg versus 25 mg) was effective in reducing nuisance (Arthritis Research Centre of Canada) side effects (17% versus 28%, p<0.05). One study also showed a trend Objective To evaluate whether there is federal health research funding and towards a reduction in side effects with every-other-week dosing rather than media discrimination against arthritis in Canada. once-weekly dosing, but this did not reach statistical significance (n=51). Methods Arthritis affects approximately 4.5 million Canadians, is the leading One randomized trial found that irsogladine maleate is effective to reduce cause of disability in Canada, causes significant morbidity and mortality and aphthous stomatitis (n=24, p<0.05). A Chinese trial found that an herbal med- is a key driver of the cost of health care in Canada. Because research indicates icine was effective, but this herbal medicine is known to have other toxic that many types of arthritis cause premature mortality, a comparison across effects. three other serious, chronic and often fatal, diseases - cancer, HIV/AIDS, and Conclusion On systematic review, there is evidence that intramuscular or diabetes mellitus - was made to determine the amount of government invest- subcutaneous MTX causes fewer nuisance side effects than oral MTX. Aside ment into research and the proportion of media coverage allocated to each. from folate, other techniques to reduce side effects do not have much evi- The number of people living with cancer, HIV/AIDS, diabetes and arthritis in dence-based support. 2005 was determined through an online search of Statistics Canada, the Public Health Agency of Canada, and the national society websites for each 57 disease. Research funding levels for each disease group were obtained Efficacy of Bazedoxifene in Reducing New Vertebral Fracture Risk in through an online search of the Canadian Institutes of Health Research Postmenopausal Women With Osteoporosis: Results From a 3-Year, (CIHR) funding reports for 2005-2006. An electronic archival search of health Randomized, Placebo- and Active-Controlled Clinical Trial and general news items, editorials, and letters to the editor printed in Canada’s J. D. Adachi (St. Joseph’s Hospital - McMaster University, Hamilton, Ontario, two national newspapers, the Globe and Mail and National Post, for the year Canada), S. L. Silverman (Cedars-Sinai Medical Center and University of 2006 was conducted; only articles specific to one of the study diseases were California, Los Angeles, CA, USA), C. Christiansen (Center for Clinical and included in the comparison. Basic Research (CCBR), Ballerup, Denmark), H. Genant (University of Results In 2005-2006, the CIHR funding for cancer, HIV/AIDS, diabetes, California, San Francisco, and Synarc, San Francisco, CA, USA), J. R. and arthritis research was $118 million, $42.4 million, $6.6 million, and $3.7 Zanchetta (University of El Salvador, Metabolic Research Institute, Buenos million, respectively. This equates to a research investment per affected Aires, Argentina), I. Valter (CCBR, Tallinn, Estonia), T. J. de Villiers Canadian of $14.20 for cancer, $731 for HIV/AIDS, $4.98 for diabetes, and (Panorama MediClinic, Cape Town, South Africa), G. Constantine (Wyeth $0.94 for arthritis. Pharmaceuticals, Collegeville, PA, USA), A. A. Chines (Wyeth In 2006, 185 articles on cancer appeared in the Globe and Mail and National Pharmaceuticals, Collegeville, PA, USA) Post, 137 on HIV/AIDS, 47 on diabetes, and 26 on arthritis. For every story Objective Bazedoxifene (BZA), a novel selective estrogen receptor modula- about their diseases, there are 4500 Canadians living with cancer, 423 liv- tor (SERM), is currently in clinical development for the prevention and treating with HIV/AIDS, 28,200 living with diabetes, and 171,000 living with ment of postmenopausal osteoporosis. We report the results of a 3-year, arthritis. Phase III study that evaluated the effect of BZA therapy on the incidence of Conclusion Discrimination is the result of prejudice or prejudicial outlook, new vertebral fracture compared with placebo (PBO) and raloxifene (RLX) in action, or treatment. Based on the study findings, it appears that one branch postmenopausal women with osteoporosis. of the federal government providing health research funding and two nation- Methods This study enrolled generally healthy postmenopausal women aged al media outlets are discriminating against arthritis in Canada. To address the 55-85 years with lumbar spine (LS) or femoral neck (FN) T-scores ≤-2.5 and discrimination in arthritis it is imperative that health research funding be com- no prevalent vertebral fractures or LS or FN T-scores ≥-4.0 with prevalent ver- mensurate with the prevalence and burden of arthritis. Increased media atten- tebral fractures. Participants were randomized to receive 20 mg/d or 40 mg/d tion to arthritis could reduce the prevalence and severity of some common BZA, 60 mg/d RLX, or PBO and received supplemental calcium (1200 mg) arthritic diseases.

Downloaded on September 27, 2021 from www.jrheum.org 59 ments were conducted every 4 wks between Wks 4 and 24. The SDAI and A Case of Actinomyces Graevenitzii Pericarditis in a Patient with CDAI were calculated for all clinical follow-up visits. Last observation car- Rheumatoid Arthritis Treated with Infliximab ried forward (LOCF) was imputed for missing scores. Major and minor Nathalie Morency (University of Montreal), Boulos Haraoui (Hopital Notre- improvements were defined as ≥13.9 and ≥6.7, respectively (CDAI), and Dame, Centre hospitalier universitaire de Montreal (CHUM) ), Eric Rich ≥17.1 and ≥6.9, respectively (SDAI). Remission was defined as CDAI <2.8 (Hopital Notre-Dame, CHUM), Jean-Luc Senecal (Hopital Notre-Dame, and SDAI <3.3. CHUM) Results A total of 298 pts in the RTX group and 201 pts in the PLC group Objective To present the first case of Actinomyces Graevenitzii pericarditis were evaluated. Baseline (BL) scores (44.6-49.7) indicated highly active dis- ever reported to our knowledge, in an anti-TNF (tumour necrosis factor) treat- ease and were not significantly different between the treatment groups. At Wk ed patient with rheumatoid arthritis (RA). 24, CDAI and SDAI scores for pts treated with RTX were lower than for pts Methods Chart of this patient has been reviewed. Literature search was con- in the PLC group. Mean changes in CDAI and SDAI scores from BL to Wk ducted on infectious pericarditis associated with anti-TNF agents and on 24 in the RTX group were -20.0 and -22.1, respectively, vs -4.5 for both in the Actinomyces Graevenitzii associated pericarditis. PLC group. The proportion of pts achieving low disease or remission was sig- Results A 54-year-old man with a 12 years history of RA on infliximab, nificantly greater with RTX vs PLC (p<0.0001), and significantly more pts methotrexate and hydroxychloroquine presented with syncope. He reported a achieved major responses (p<0.0001) for both the SDAI and CDAI. CDAI history of common cold two weeks earlier lasting for few days. Immediately and SDAI remission rates in the RTX group were significant vs. PLC, 6% vs. after the resolution of his symptoms he started complaining of dyspnea 1% and 5% vs. 0%, respectively. accompanied by nausea, vomiting and anorexia. All drugs were continued Conclusion RTX + MTX produced a significantly larger reduction in disease until the hospitalisation and his scheduled infusion of infliximab was given 4 activity (measured by CDAI and SDAI scales) compared with PLC + MTX, days prior to admission. as well as having higher proportions of pts with clinically meaningful On admission, clinical examination was mostly normal except for tachy- improvement. These simplified scoring methods may be useful for determin- cardia at 107 beats/min. Investigation revealed a white cell count of 16.4 ing RTX efficacy in clinical practice. x 10 9/l and a hepatic impairment withAST at 1263 U/l,ALT at 1126 U/l, LDH at 1736 U/l and INR at 2.1.Acute renal failure was noted with a cre- 61 atinine of 402 umol/l. He had normal troponine level and a normal abdom- Evaluation of the Success of a Transition Clinic Established for Young inal ultrasound. Diagnosis of pericarditis was made when echocardiogra- Adults with Rheumatic Diseases phy showed heterogeneous pericardial effusion. The patient developed Krystina Kiefer (Alberta Childrens Hospital), Nicole LaBrie (University of pulsus paradoxus and a pericardiocentesis was undertaken. A purulent Calgary), Paivi Miettunen (Alberta Childrens Hosptial), Nicole Fahlman pericardial fluid was extracted and Actinomyces Graevenitzii was identi- (University of Calgary), Nicole Johnson (Alberta Childrens Hospital), Anne fied on cultures. The empirical vancomycin was stopped and initial peni- Marie Crawford (University of Calgary), Terri Lupton (University of cillin treatment was changed for clindamycine after a rash developed. Calgary) Patient needed one more pericardiocentesis and a pericardiotomy during Objective Transition clinic for Young Adults with Rheumatic Diseases the hospitalisation. Despite treatment, he developed constrictive (YARD) was established in a tertiary care hospital in February 2006. A sys- pericarditis. tematic review of the clinic was performed to evaluate the success of the clin- We did not find any case of pericarditis associated with Actinomyces ic regarding achieving the following goals: to foster medical independence in Graevenitzii in the literature. Two other cases of infectious pericarditis asso- patients moving from the pediatric setting to the adult health care setting, to ciated with anti-TNF have been reported, one due to peptostreptococcus and provide vocational support, to minimize patients lost to follow-up and to pre- the second due to Staphylococcus aureus. vent admissions for unpredicted disease flare. Conclusion We suspect anti-TNF treatment to be a major contributing factor Methods A retrospective chart review was preformed of all patients seen at in this Actinomyces Graevenitzii pericarditis. This case showcases yet anoth- YARD between February 2006 and August 2007. Data collected included er unusual infection in the context of anti-TNF therapy and highlights the number, age, diagnosis, medical treatment with biologic agents/intravenous importance of patient education and the high degree of suspicion needed medications, educational or work status, and number of total and missed vis- when faced with a patient with new complaints. its of patients. Results A total of 107 patients were transitioned. The diagnoses (number 60 of patients) included juvenile idiopathic arthritis (35), spondyloarthropa- Improved Clinical and Simplified Disease Activity Index (CDAI, SDAI) thy (29), mixed connective tissue disease (6), uveitis (6), systemic lupus Scores with Rituximab in Patients with Rheumatoid Arthritis (RA) and erythematosus (5), psoriatic arthritis (4), juvenile dermatomyositis (2), an Inadequate Response to TNF Inhibitors vasculitis (3), chronic recurrent osteomyelitis or avascular necrosis (5) or Josef Smolen (Medical University of Vienna, Vienna, Austria), Alfred other (12). 13 patients received biologics, and 9 received IV medications Cividino (McMaster University), Arthur Kavanugh (UCSD, La Jolla, CA), (methylprednisolone, IVIG, bisphosphonates, remicade). 42 patients Hans Peter Tony (Universitätsklinikum Wurzburg, Wurzburg,Germany ), attend university/post-secondary education, 43 high school, 1 was on Maria Greenwald (5Desert Medical Advances, Palm Desert), Salvatore De maternity leave, and 20 work full time. One patient was on disability but Vita (University of Udine, Udine, Italy), Richard Brasington (Washington pursuing part-time education. There were only 19/237 “no-show” visits, School of Medicine, St Louis, MO), Daniel Aletaha (Medical University of however several reminders were required for many patients. All patients Vienna, Vienna, Austria), Anne Marie White (Roche Products Ltd, Welwyn were seen on their own after the first YARD visit. All patients received Garden City, United Kingdom), Eva Hessey (Roche Products Ltd, Welwyn allied health care support (nursing, physiotherapy, and social work with Garden City, United Kingdom) vocational counseling). No hospitalizations were required for uncon- Objective To evaluate the efficacy of rituximab (RTX) compared with place- trolled disease. bo (PLC) using CDAI and SDAI scores in patients (pts) with rheumatoid Conclusion The number of “no shows” was much lower than anticipated arthritis (RA) who have had an inadequate response (IR) to ≥1 TNF inhibitor from literature reviews, however allied health support was required to insure therapies. clinic attendance. 21 % of patients received complex medications (biologics Methods Pts with a prior IR to TNF inhibitors and receiving background and/or IV medications), and all patients attended clinics independently. The methotrexate (MTX; 10-25 mg/week [wk]) received a single course of either majority of patients were engaged in education or employment. Our results RTX 1000 mg or PLC (IV) on Days 1 and 15, with concomitant glucocorti- suggest that regular clinic attendance was helpful in preventing unexpected coids. Key inclusion criteria have been previously reported . Clinical assess- hospital admissions for disease flare.

Downloaded on September 27, 2021 from www.jrheum.org 62 number of unique haplotypes for each window for Toronto and Alberta pop- The Psoriasis and Arthritis Screening Questionnaire (PASQ): A Sensitive ulations. 361 Caucasian controls from Toronto and 401 Caucasian controls and Specific Tool to Diagnose Psoriatic Arthritis Patients with High from Alberta were assessed for the number of haplotypes using PHASE. Correlation to the CASPAR Criteria. The Alberta controls were healthy, unrelated, controls with Caucasian sur- Majed Khraishi (Nexus Clinical Research and Memorial University of names. The Toronto controls were unrelated Caucasian individuals from Newfoundland), Ian Landells (Nexus Clinical Research and Memorial Toronto. The ethnic composition of the Toronto controls was broadly University of Newfoundland), Catherine Heale (Memorial Univeristy of European. Newfoundland and Labrador), Gerry Mugford (Memorial Univeristy of Results The number of haplotypes in Toronto and Alberta for the four win- Newfoundland and Labrador), Belinda Grouchy (Nexus Clinical Research) dow sizes are as follows: 6 marker window – 820 Toronto haplotypes vs 744 Objective To examine the modified PASQ with respect to its sensitivity and Alberta haplotypes (difference 76); 8 marker window – 1261 Toronto haplo- correlation to the CASPAR criteria for diagnosing psoriatic arthritis. types vs 1115 Alberta haplotypes (difference 146); 10 marker window – 1680 Methods An evaluation of a modified PASQ, containing ten questions and Toronto haplotypes vs 1453 Alberta haplotypes (difference 227) and 12 mark- a diagram for patients to label where they have experienced joint er window – 2004 Toronto haplotypes vs 1710 Alberta haplotypes (difference swelling/pain in a rheumatology and a dermatology clinic based popula- 294). Thus the Toronto population contains more unique haplotypes for each tion of psoriasis/psoriatic arthritis patients. Scores were obtained individ- window size that are absent in Alberta population. ually for the PASQ and diagram, as well as cumulatively, to a maximum Conclusion Investigators planning case-control genetic association studies score of 15. should be aware of the population differences between Toronto and Alberta The CASPAR criteria for each subject were assessed through chart review. To and should take this into account if combining these populations in genetic assess the utility of the PASQ in detecting subjects who meet the CASPAR association studies. Careful consideration should also be given to how the criteria, the receiver operating curve (ROC) using MedCalc® software was controls are selected. obtained. Descriptive statistics were obtained by SPSS. Results Data was collected on 45 patients (53% male) citing a personal his- 64 tory of psoriasis and arthritis. Mean age: 51.8 ± 11.3, duration of skin disease: Oral Contraceptives and Systemic Lupus Erythematosus, Current 20.4years ± 14.2, 69% of those surveyed had a family history of psoriasis, Practice in Hamilton 82% had a family history of arthritis. 4 subjects did not meet the CASPAR cri- Sanjay Dixit (McMaster University), S. Waserman (McMaster University), teria. Analysis of the PASQ scores with the ROC curve [Area under curve Nader Khalidi (McMaster University) (AUC) = 0.854, 95% C.I: 0.716 to 0.941, p=0.0001] indicated a total score of Objective To evaluate the current practice of prescribing OCS in lupus 6 yielded 82.93% sensitivity, 75% specificity, with a positive likelihood ratio patients in Hamilton and to assess if it was associated with an increase in (+LR) of 3.32, and a negative likelihood ratio (-LR) of 0.23. Analysis of the lupus flare. cumulative score [AUC = 0.902, 95% C.I: 76.9 - 97.2, p=0.0001] yielded a Methods A retrospective review of charts along with Electronic patient labo- cutoff score of 9, with 90.24% sensitivity, 75% specificity, and a +LR of 3.61, ratory data collection from September 1996 to September 2006 was conduct- and -LR of 0.13. ed. Patient characteristics (age, obstetrical history, date of SLE diagnosis, cri- Conclusion Preliminary data suggests that the modified PASQ, with high sen- teria for SLE diagnosis, duration of disease, smoking history, thrombosis his- sitivity, is effective at detecting patients who meet the CASPAR criteria for tory), current and previous use of the OCP, anticoagulation, and treatments for PsA. Continuing studies are ongoing to check the sensitivity in early psoriat- SLE were assessed. ic arthritis, as well as the utilization of this modified PASQ in identifying Results 490 patients identified. 188 charts reviewed. 43 patients qualified for patients in a dermatology or a general practice setting that are at high risk of study. developing psoriatic arthritis. The total number of SLE patients with prior use or currently using OCS was 4 (9 % of total SLE patients reviewed). Six patients had positive 63 antiphospholipid antibodies while 17 had renal involvement. 2 patients Marked Differences in Genetic Structure of Two Geographically Distinct with positive antiphospholipid antibodies had used OCS at some point in Canadian Populations the past and 1 patient had been advised that OCS was acceptable during a Mohammed Uddin (Memorial University of Newfoundland), Walter clinic visit if warfarin control was not subtherapeutic. There were no doc- Maksymowych (University of Alberta), Robert Inman (University of umented discussions of the risks associated with the use of OCS or the Toronto), Dafna Gladman (University of Toronto), Mitch Sturge (Memorial avoidance of OCS with positive antiphospholipid antibodies. From the University of Newfoundland), Lynette Peddle (Memorial University of cohort of patients with renal involvement, 2 had used estrogen containing Newfoundland), Nicky Roslin (University of Toronto), Proton Rahman OCS in the past while 5 patients had used a PCS or progesterone depot. (Memorial University of Newfoundland) From the patients with renal involvement, one chart documented a discus- Objective Complex rheumatic diseases including spondyloarthritis exhibit a sion of the avoidance of OCS during an assessment at the maternal fetal strong genetic component. Genetic association studies using a case control medicine clinic. approach havebeen frequently utilized for identifying disease related genes. Conclusion Our study did not find an increase in lupus flare with the use However it is also recognized that large cohorts of cases and controls are of OCS. Though the study was limited for the part due to inadequate docu- required to account for the low allele frequencies and modest odds ratios of mentation of contraception practices in the charts. A standard approach must the SNPs/haplotypes that are being identified. To enhance sample sizes, cases be shared by those taking a history and advising patients with SLE of child- and controls are being pooled from multiple geographic centres in Canada. A bearing age. Since the components of sexual history taking and contracep- problem with the case-control design is that the SNP or haplotype frequencies tive counseling are not always in the day-to-day scope of practice for vary between ethnic or geographic populations. If the case and control popu- rheumatologists and immunologists, education is crucial in caring for lations are not well matched for ethnicity or geographic origin then false pos- patients who have positive antiphospholipid antibodies, active renal involve- itive association can occur because of the confounding effects of population ment or who are taking teratogenic drugs. Recommendations on when to stratification. We examined control populations from Alberta and Ontario in refer high-risk patients with SLE for further contraception counseling must order to determine the variability in haplotypes noted between these two be developed. This study also highlights the importance of proper chart Canadian populations. maintenance and documentation. We are currently conducting second part of Methods Control samples previously genotyped for 41 SNPs in the IL-1 clus- the study with telephone interviews with the patients to further assess the ter region of chromosome 2q for an ankylosing spondylitis study were reana- safety of OCS in lupus and OCS prescription practice in patients with lupus lyzed. Sliding windows of 6, 8, 10 and 12 markers were used to calculate the in Hamilton.

Downloaded on September 27, 2021 from www.jrheum.org 65 (1.54,5.55), neck stiffness an OR of 3.39 (1.80,6.39), back pain an OR of 2.96 PIAF — Programme d’Intervention Apres Fracture (1.43,6.11) and back stiffness an OR of 3.30 (1.50,7.28). Adjusted for disease Diane Ferland (CH Maisonneuve-Rosemont), JP Mathieu (CH Maisonneuve- duration, AoAS was associated with higher BASFI scores, fatigue severity Rosemont), Pascal Venditolli (CH Maisonneuve-Rosemont), Ngoc Vyen scores and AS Quality of Life measures. Troung (CH Maisonneuve-Rosemont), Donald Breton (CH Maisonneuve- Conclusion If JoAS represents the same disease process as AoAS just pre- Rosemont), Pascale Garneau (CH Maisonneuve-Rosemont), Michel senting at an earlier age, it would be expected that the pattern of disease Zummer (CH Maisonneuve-Rosemont) expression would be comparable between JoAS and AoAS if corrected for Objective To improve the care of individuals who had suffered an atraumat- disease duration. This was not the case: JoAS follows a clinical course dis- ic fracture. The ROCQ (Recognizing Osteoporosis and its Consequences in tinctive in its axial:peripheral pattern. Furthermore, these clinical features are Québec) study found that at our centre (CH Maisonneuve-Rosemont), only dictated by factors other than male gender and HLA-B27 and warrant further 12% of 112 pateints had a diagnosis and treatment for osteoporosis in the sub- investigation. sequent year. We evaluted the impact of a well-defined care path to increase the recognition and evaluation of patients in our centre with a low trauma 67 fracture. The RemiTRAC INFUSION Registry: Safety and Management of Methods A fracture intervention program (PIAF) was established at our cen- Infliximab Infusions in a Real-life Setting tre. A dedicated coordinator identified patients at the fractrue clinic (age ≥ 40; Denis Choquette (Institut de Rheumatologie de Montreal), Rafat Faraawi low trauma fracture of wrist, proximal humerus, hip or vertebra; osteoporosis (Kitchener, ON), Majed Kraishi (Arthritis Research Centre), William Bensen status). These patients were then referred by the orthopedic surgeon to the (McMaster University), Francois Nantel (Schering-Plough) osteoporosis clinic (COMO) where they were evaluated and a treatment plan Objective and Method The RemiTRAC INFUSION is a Canadian registry forwarded to the patient’s family physician. in which patients receiving Infliximab (IFX) are followed prospectively to Results Since program inception, between March and November 2007, 290 document medication use, adverse events, infusion reactions and management patients were screened and 185 (64%) referred to COMO. To date 111 of infusion reactions. The registry started in August 2005. pateints have been or are awaiting evaluation. At present, 69 patients were Results After 2 years, 383 patients were enrolled of whom 192 (54%) were at evaluated, 54 (78%) female, 29 smokers and 6 receiving corticosteroids. their first IFX infusion. A total of 2519 infusions were recorded with a mean Bone mineral density (BMD) results indicated that only 18% had a t-score < of 6.7 ± 4.1 infusions per patient representing 282.3 years of exposure. The -2.5 and 28% had a normal BMD. Reasons for being referred and not evalu- majority of patients (n = 300, 78%) had rheumatoid arthritis (RA), ankylos- ated included: wished follow-up with GP (18), known osteoporosis (17), ing spondylitis (AS) or psoriatic arthritis (PsA). Interim results show that the patient refused (15), dementia (10), MD refused (9), patient in long-term care incidence of infusion reactions in all patients was low (56/2519 or 2.22%) and (4), language (2) and death (2). almost all reactions were mild to moderate in severity (52/56). No serious Conclusion Previous fracture is an important predictor of future fractures. A infusion reactions were recorded in the study. In RA patients, the incidence specific intervention program with a dedicated coordinator and a defined care of infusion reactions was 2.8% (44/1548) in contrast to only 0.7% in AS path improved the recognition and evaulation of patients in our centre with patients (3/453) and 0.6% in PsA patients (1/155). In all patients, most infu- low trauma fracture from 12% to 64%. sion reactions were managed by slowing the infusion rate (30%), infusing Supported by an unrestricted grant from the Alliance for Bone Health. saline (71%) and/or by treatment with anti-histamines (70%), steroids (29%) or acetaminophen (13%). The majority of patients (>70%) with infusion 66 reactions were subsequently pre-treated with anti-histamines, steroids or acet- When B27-positive Boys Grow Up: The Differing Clinical Courses of aminophen. However, only acetaminophen appeared to decrease the overall Juvenile- and Adult-onset Spondyloarthritis incidence of infusion reactions. Patients who were on methotrexate upon Finbar O’Shea (Toronto Western Hospital), Eleanor Boyle (Toronto Western study entry did not appear to have more infusion reactions than those who Hospital), Shirley Tse (The Hospital for Sick Children), Ronald Laxer (The were not (2.2% in both groups). Patients who were on corticosteroids upon Hospital for Sick Children), Robert Inman (Toronto Western Hospital) study entry had a 4% incidence of infusion reaction (26/655) in contrast to Objective In terms of understanding the pathogenesis and clinical course of only 1.6% (30/1864) in subjects who were not. Serious adverse events were ankylosing spondylitis (AS), juvenile-onset AS (JoAS) has been regarded as reported in 45 patients and included diarrhea, pneumonia, cellulitis, tachycar- a critical aspect of the disease for both prognostic and genetic studies. But an dia and urinary tract infections. There were 2 malignancies, one breast cancer important unresolved issue has been whether JoAS by a distinctive clinical and a fibroma of the uterus. evolution is a clinical entity in its own right, or just an earlier onset variant of Conclusion This registry shows that, in a real-life setting, infusion reactions its adult-onset AS (AoAS) counterpart. In this study, we address this unre- to infliximab occur at a low incidence, are mainly mild to moderate in sever- solved issue. ity and are easily managed by health care professionals. Methods The patients were drawn from the clinical database of the Spondylitis Clinic in a large teaching hospital. Patients are evaluated accord- 68 ing to a standard protocol in which demographic, clinical, radiographic and Arthritis Consultation Utilizing Telehealth in Southern Alberta; a 2 Year laboratory variables are recorded at regular intervals. All patients with a Pilot Project symptom onset of <16 years were identified from the database and compared Sharon LeClercq (University of Calgary), Liam Martin (Universioty of to all AS patients with a symptom onset >17 years. Odds ratios (OR) were cal- Calgary), Sujata Connors (Calgary Health Region) culated and adjusted for disease duration and current age. Objective A 2 year pilot project utilizing Telehealth [TH], videoconferencing Results 84 JoAS and 183 AoAS patients were compared. Mean age at symp- via telephone lines, was created in order to address the need for improved tom onset was 12.8 years for JoAS and 26 years for AoAS. There were no dif- access and care for arthritis patients in Southern Alberta. ferences in gender ratio (% male: JoAS: 81; AoAS: 79), nor in HLA-B27 pro- Methods Two distant Alberta sites, Pincher Creek [PC] and Rocky Mountain file (% positive: JoAS: 75; AoAS: 81). Family history of AS, Psoriasis, uveitis House [RMH] were selected based on distance, population, proximity to First or inflammatory bowel disease did not differ between the two groups. The Nations communities and familiarity with the local family physicians. Seven axial/peripheral pattern of disease at presentation differed: an exclusively family physicians were trained in basic joint examination on-site utilizing peripheral pattern was seen in 26% JoAS but in only 4.6% AoAS (p<0.0001). local arthritis patients and in the arthritis clinics in Calgary. Five Calgary There were no differences in disease activity (BASDAI, ESR, CRP) at the rheumatologists were engaged to participate in the TH clinics. Referrals were time of assessment. Adjusted for disease duration, axial features were more triaged to ensure «arthritis only» consultations. Monthly TH clinics were prominent in AoAS than JoAS. In AoAS, neck pain had an OR of 2.93 established at each site. During the consultation the patients’ history was

Downloaded on September 27, 2021 from www.jrheum.org obtained directly and a physical examination performed by the trained by primary care clinicians, currently proposed clinical discriminators per- physcian under direct observation by the rheumatologist. Pertinent lab results formed poorly in correlating with radiographic changes in the SIJ. Further and radiographs were reveiwed. Diagnoses, treatment plans and follow-up study is warranted in this important area of diagnostics in spondyloarthro- plans were discussed and implemented. Once each year, the local physicians pathy. were retrained on site with patients that they had found difficult to assess. Results During the 2 years, 195 patients were assessed; 113 new patients and 70 82 followup patients. Telehealth review and treatment advice was provided Development of a Screening Tool for Inflammatory Arthritis Referrals on 35 additional patients who did not personally attend the clinic. The major- Using the Sensitivity and Specificity of Pain Diagrams for Diagnosis in ity of patients had inflammatory arthritis, including five early inflammatory Rheumatic Diseases in a Large Referral Cohort arthritis patients and five established RA patients who required biologic ther- Angela Caines (University of Western Ontario, London, ON), Nooshin apy. Additional diagnoses included osteoarthritis, seronegative arthritis, Samadi (University of Western Ontario, London, ON), Janet Pope ankylosing spondylitis, polymyalgia rheumatica and crystal arthritis. No (University of Western Ontario, London, ON), Andrew Thompson patients were required to travel to Calgary due to inadequacy of the TH (University of Western Ontario, London, ON) process. Additional educational events such as formal evening educational Objective Early aggressive treatment of inflammatory arthritis has been sessions for the family physicians and allied health professionals, family and shown to retard joint destruction, so a means of identifying such patients early public forums, and mid day formal sessions with mulitple First Nations sites is paramount. Pain diagrams have been widely used in the literature to eval- in southern Alberta with TH capabilities. uate both pain intensity and physical exam findings, and even assist in diag- Conclusion The project evaluation was positive from patients, family physi- nosis. Their use however, has been evaluated primarily in chronic pain con- cians, and rheumatologists. A critical key for success is the MSK initial train- ditions [fibromyalgia (FM), chronic back pain]. The objectives were to deter- ing and reinforcement of the family physician at the distant site. Arthritis mine the sensitivity and specificity of patterns on the pain diagrams in a large consultation via videoconferencing can extend our capacity and ability to pro- rheumatology cohort. vide timely and appropriate care for arthritis patients. Methods All new patient charts referred to 2 rheumatologists, between the years 2000-2006, were included and eligible if a pain diagram had been com- 69 pleted, the patient was not previously seen by a rheumatologist (hence had no Examination of the Association of Clinical Descriptors with diagnosis), and was 18 years of age or older. Pain diagrams were organized Radiographic Findings in a Primary Back Pain Cohort into groups based on the location of joint areas and/or soft tissue areas com- Finbar O’Shea (Toronto Western Hospital), Carlo Ammendolia (Canadian pleted by the patient (herein referred to as patterns). Memorial Chiropractor College), Eleanor Boyle (Toronto Western Hospital), Results 1101 patients were included. Five major patterns evolved: soft David Salonen (Toronto Western Hospital), Cindy Peterson (Canadian tissue (widespread pain or regional pain such as an entire arm) n=236, Memorial Chiropractor College), William Hsu (Canadian Memorial symmetrical articular n=647, asymmetrical articular n=136, monoarticu- Chiropractor College), Robert Inman (Toronto Western Hospital) lar n= 35, and back n= 46. Four hundred and eighty had inflammatory Objective With the advent of new therapies for inflammatory back pain (IBP) arthritis of whom 121 had RA, 35 PsA, 46 spondyloarthropathies, and 63 there has been renewed interest in identifying clinical features that might crystal arthropathy. FM/chronic pain also occurred in 63 and 25 had accurately predict radiographic changes in the spine and sacroiliac joint (SIJ). PMR. As would be expected, RA often had a polyarticular symmetrical This is particularly challenging in primary back pain cohorts and the present pattern and FM had a soft tissue pattern. The sensitivity, specificity, pos- study was undertaken to examine these clinical-radiographic relationships in itive predictive value (PPV) and negative predictive value (NPV) are as that setting. listed. Methods All lumbar spine and AP pelvis radiographs taken over a 3-year Conclusion This is the first large referral study to determine the characteris- period for the evaluation of back pain at a major chiropractic college were tics of pain diagrams in a rheumatology referral practice. These patterns retrieved and evaluated. The radiographs were reviewed and a consensus could help to prioritize patients with suspected inflammatory conditions report was generated by 3 readers with respect to inflammatory or degenera- adding to the demographics, history and labs. We are testing the diagrams on tive features in the SIJ. The clinical notes of this cohort were reviewed, and patients referred to our clinic whereby the patient completes the form in the data were extracted by means of a pre-determined template. The clinical fea- referring doctors’ offices. We suspect this will increase our accuracy of pri- tures were evaluated to assess their performance as discriminators between oritizing early RA. the radiographic subsets. Results 315 patients (173 male, 142 female) between the ages of 18 – 60 had 71 radiographs performed for the evaluation of back pain. Of this cohort, 274 A Meta-analysis of Complementary and Alternative Treatments (CAM) clinical records (156 Male, 118 Female) were available. These were retrieved Deanne Malenfant (University of Western Ontario), Michelle Catton and reviewed. 213 patients (124 Male, 89 Female) having back pain for ≥ 3 (University of Western Ontario), Janet Pope (University of Western Ontario) months and radiographs were identified. Radiographic findings in the SIJ of Objective Raynaud’s phenomenon (RP) is reversible vasospasm of digits this cohort were as follows: 143 (67%) normal, 53 (25%) degenerative, 17 which is often painful. Conventional treatment is limited due to side effects (8%) inflammatory. Among the 53 degenerative SIJ x-rays there was a signif- such as hypotension and flushing with calcium channel blockers and other icant difference between the number of males (23) and females (30) (p=0.04). vasodilators, and complementary and alternative treatments (CAM) are wide- The following clinical features were evaluated: (i) nocturnal pain, (ii) ly used by the population. Thus, finding effective and well tolerated CAM for improvement with exercise, (iii) improvement with rest, (iv) insidious onset, the treatment of RP would be advantageous. (v) extra-articular features of spondyloarthropathy, (vi) location and radiation Methods Using Medline, Embase and AMED randomized controlled trials of pain. Of these clinical descriptors, none were associated with the radi- (RCTs) of CAM in RP treatment were obtained. The trials were separated in ographic findings, with the single exception that pain in the buttock was sig- categories of similar interventions and these were meta-analyzed together. nificantly associated with inflammatory sacroiliitis (p=0.02). The clinical Trials were included if randomized, controlled with a placebo or other com- review also demonstrated that neither being overweight (body mass index > parator, and where RP was an outcome. All analyzable outcome measure- 25) nor pregnancy history was associated with degenerative or inflammatory ments were recorded. changes in the SIJ. Results The search yielded 33 studies, but 12 were excluded because of Conclusion Clinical features which might serve as surrogate markers for IBP methodological problems or unextractable data. The included trials were are a high priority in improving early detection of ankylosing spondylitis. Our divided into 10 subcategories: acupuncture (n=2 trials), biofeedback (n=5), findings indicate that in a back pain cohort characteristic of that which is seen hypnosis, laser (n=3), therapeutic gloves, essential fatty acids (n =3), anti-oxi-

Downloaded on September 27, 2021 from www.jrheum.org dants (n =2), glucoseaminoglycans, ginko biloba, and l-arginine (n=2). 73 Many categories did not have enough trials to do a meta-analysis and most Sustained Improvement with Repeated Courses of Rituximab in Patients were not positive, of poor quality and done prior to 1990. The biofeedback with Rheumatoid Arthritis and an Inadequate Response or Intolerance meta-analysis was negative for the change in frequency, duration and to One or More TNF Inhibitors severity of RP attacks, and in fact it favored control (sham biofeedback) Edward C. Keystone (University of Toronto), Janet Pope (University of with p<0.02. The therapeutic glove treatment (n=1 trial) favored active Western Ontario), Roy M. Fleischmann (Metroplex Clinical Research Center, treatment in both change in visual analogue scale (VAS) and a validated Dallas, TX), Paul Emery (Leeds General Infirmary, Leeds, United Kingdom), upper extremity measurement [DASH] (p<0.00001). The other meta- Andrew Chubick (Baylor University Medical Center, Dallas, TX), Maxime analysis that yielded positive results was laser vs sham (131 subjects in R. Dougados (Hopital Cochin, Paris, France), Andrew R. Baldassare (St total) which resulted in a change in frequency over two weeks [weighted Louis University, St Louis, MO), Joan M. Bathon (Johns Hopkins University, mean difference [WMD] 1.18 (CI: 1.06, 1.29)] and severity of attacks (on Baltimore, MD), Eva Hessey (Roche Products Ltd, Welwyn Garden City, a scale of 1-10) [WMD 1.98 (CI: 1.57, 2.39)], p<0.05. No significant dif- United Kingdom), David Hagerty (Biogen Idec, San Diego, CA), Simon ferences were found in the nutritional supplements that were studied. Most Cooper (Roche Products Ltd, Welwyn Garden City, United Kingdom) trials did not study side effects so the risk to benefit is not available for sev- Objective To provide further analysis of the long-term efficacy of repeated eral treatments. courses of rituximab (RTX) therapy in patients (pts) with active rheumatoid Conclusion There is a need for well designed trials of CAM in RP. The cur- arthritis (RA) who had a previous inadequate response or intolerance to tumor rent literature is not conclusive enough to make educated decisions except that necrosis factor (TNF) inhibitors. biofeedback does not work for RP, special therapeutic gloves seem to help and Methods Pts received repeated courses of RTX in an ongoing open-label laser is effective. extension to Phase II and III studies. Each course of RTX consisted of two infusions of RTX (1000 mg x 2) 2 weeks apart; prior to each infusion, all pts 72 received 100 mg IV methylprednisolone, with oral glucocorticoids adminis- The Relationship Between Healthcare Access and Disease Activity and tered between the two infusions. Eligibility for repeat treatment: predefined Damage in a Multiethnic Cohort of Systemic Lupus Erythematosus improvement (≥20% reduction of SJC and TJC), residual disease activity (SLE) Patients: The 1000 Canadian Faces of Lupus Study (defined as ≥8 SJC and TJC), in combination with the judgment of the treat- Genevieve Law (University of Western Ontario), Janet Pope (University of ing physician. Placebo-treated pts could also enroll and receive RTX. In this Western Ontario), Christine Peschken (University of Manitoba) completer analysis, all efficacy outcomes were assessed relative to the origi- Objective Access to medical care, including the proximity of healthcare nal pretreatment baseline. providers and medication costs, is a factor that may influence health status. It Results Data are from 571 RA pts with a prior inadequate response or intol- is unclear whether problems with access can predict clinical outcomes in erance to ≥1 TNF inhibitors had been exposed to repeated courses of RTX lupus. We have a unique situation in Canada with global healthcare, but there (1000 mg x 2 for all courses) in the clinical program. Of these, 210 pts had are still potential barriers to care. This study aimed to determine whether received ≥3 courses (C) of RTX. The median period between the treatment patient identified care barriers are associated with increased disease activity courses was 37.9 weeks for C1-C2 and 42.1 weeks for C2-C3. Efficacy data and damage in this prospective, multi-centre, multiethnic SLE cohort. We were available for 97 pts who, at the time of analysis, had reached at least 24 also compared concordance between care barriers as reported by the patient weeks’ follow-up post-C3. Comparison of efficacy between treatment cours- and specialist. es at 24 weeks following C1, C2, and C3 showed sustained efficacy for all Methods Data from SLE patients in 14 Canadian centers with annual visits outcomes specifically ACR50 in 36%, 48%, and 48%, respectively and were collected, including demographics, socioeconomic status, treatment, ACR70 in 11%, 26%, and 29%, respectively. Remission, defined as a disease activity (SLEDAI, SLAM), and damage (SLICC). Patient reported DAS<2.6 was shown in 6%, 14%, and 12% of patients having received C1, access to care included availability of physician, financial barriers, and per- C2, and C3, respectively. In patients exposed to C1, C2, and C3, the mean ceived difficulties in accessing rheumatology clinics and medications. DAS28 change from original baseline was -2.39, -2.94, and -3.10, respective- Healthcare access variables where problems for >15% of the cohort were used ly. in analyses. Conclusion These results indicate that repeated courses of RTX provide Results 636 patients were enrolled with ethnic groups being Caucasian ongoing efficacy relative to original baseline in pts with active RA who had (65%), Native American (6%), Asian (20%), and African (9%). Availability responded inadequately to previous TNF inhibitors and who remain on RTX of a rheumatologist was not identified as an issue but the majority report- 24 weeks after C3. ed having to travel to another community for specialist care. Barriers to medical care for some SLE patients included travel to a rheumatologist’s 74 office (TRheum), waiting to see a rheumatologist (WaitRh), and cost of The Cost-Effectiveness of Anti-TNF Agents in Rheumatic Disorders as medications (CMed). When stratified by ethnicity, there were statistically Measured by the Minimally Clinical Important Difference (MCID) in the significant associations between ethnicity and TRheum (p=0.031) as well Health Assessment Questionnaire (HAQ) as ethnicity and Cmed (p=0.033). In univariate analyses, TRheum, WaitRh, Lillian Barra (University of Western Ontario), Janet Pope (University of and Cmed were not significantly related with any measure of morbidity. Western Ontario), Michael Payne (University of Western Ontario) We re-examined the data within the Caucasian group to eliminate ethnici- Objective To determine the cost-effectiveness of anti-TNF medications for ty as a possible explanation for the findings and there was a correlation the treatment of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and between Cmed as a barrier and disease activity (initial SLAM score), Ankylosing Spondylitis (AS) using the Health Assessment Questionnaire p=0.046. Doctors identified only half the patients who had access to med- (HAQ) within a Canadian context. ication problems (r=0.2, p=0.000) and doctors were poor at identifying Methods We created a database compiling all patients with RA, PsA or AS most care barriers. treated with anti-TNF agents (Etanercept, Infliximab and/ or Adalimumab) at Conclusion Our recruitment strategy was a limitation as patients entering the St. Joseph’s Hospital in London, Ontario. Patient characteristics, duration of cohort had access to a lupus specialist. However, this would allow for a best treatment, baseline HAQ scores prior to treatment and subsequent yearly case scenario, but despite access to a specialist, many barriers were found. HAQ scores were collected. If treatment was terminated, reasons were Medication cost was related to SLE disease activity. We cannot determine if recorded. The cost based on MCID of HAQ (% of patients with >0.2 this was cause or effect. Ongoing research may answer this question. Care improvement) was calculated using the direct cost of the medication (~$20 barriers are important for lupus outcomes and are grossly under-estimated by 000/annum). We determined if the MID HAQ improvement would be clini- physicians. cally relevant and related to important future outcomes.

Downloaded on September 27, 2021 from www.jrheum.org Results The mean age was 55, with 12 years of disease and the mean base- 76 line HAQ was 1.4. The change in HAQ at years 1, 2 and 3 were: —0.31(n = What Is the Relationship Between Disease Activity, Severity and Damage 214), —0.24 (n = 118) and —0.27 (n=73) for a cost to achieve MCID of $37 in a Large Canadian Scleroderma Cohort? Results from the Canadian 526, $44 348 and $41 142 respectively. In RA, the change was —0.35 at year Scleroderma Research Group (CSRG) 1 (n = 123), —0.24 at year 2 (n = 78) and —0.28 at year 3 (n = 51), costing Xiangning Fan (University of Western Ontario, London, ON), Janet Pope $38 710, $46 897 and $42 500 respectively. Similarly, HAQ scores in PsA (University of Western Ontario, London, ON), Murray Baron (Jewish were changed by —0.375 (yr 1; n = 41), —0.239 (yr 2; n = 25) and —0.280 General Hospital, Montreal, PQ) (yr3; n = 17) with associated costs of $34 167, $45 455 and $37 778 respec- Objective Many large data sets exist in scleroderma (SSc) which are often tively. For AS, the HAQ score changed by —0.202 (n = 21) for a cost of $42 single centre and skewed towards more severe disease activity. Predictors of 000 in year 1. damage are often determined from highly specialized centres or from hospi- Conclusion We obtained real-world data on the cost-effectiveness of anti- tal data bases which are not generalizable to most SSc patients. The CSRG is TNF drugs using the HAQ score (% achieving > MCID), which is known to unique in that at multiple sites, SSc patients are entered into a database pos- be an excellent predictor of work disability, morbidity and mortality. HAQ sibly with less bias towards severe scleroderma, which is closer to the true scores decreased with treatment and were sustained throughout the 3 years of population of scleroderma. We hypothesized that there is a relationship follow-up. There was no difference between the diseases studied. between disease activity and severity and damage, but that severity would be Approximately 50% of patients on anti-TNF agents achieved the HAQ MCID more strongly related to damage. for a NNT of 2. The changes in HAQ scores reported here are less than in Methods We performed correlations and compared the relationship between RCTs (but the patients started with higher mean HAQs than most antiTNF tri- physician rated activity, severity and damage in SSc. Predictors of damage als) and therefore cost-effectiveness analyses modeled on RCTs should be and severity with respect to age, disease type and duration and organ systems cautiously interpreted. were studied. Results 615 patients with SSc, 87% women, mean age 55 yrs, mean 8.56 yrs 75 disease duration, 41% with diffuse scleroderma were studied. The mean (SD) Long Term Safety of Methotrexate in Rheumatoid Arthritis; a Systematic patient global health score was 3.6 (2.4) on 10 cm VAS, and disease activity Literature Review was 3.6 (2.6). Physician rating of SSc severity, activity and damage was 2.8 Carine Salliot (Saint Louis Hospital, Paris ), Claire Bombardier (University (2.2), 2.3 (2.0), and 3.4 (2.4) implying damage had the highest mean rating. Health Network), Desiree van der Heijde ( Dept of Rheumatology, Leiden From correlational analyses, it was found that damage was related to both University Medical Center, Leiden, Netherlands) severity and activity, r=0.725, p<0.001, and r=0.577, p<0.001, respectively, Objective To perfom a systematic literature review regarding long term safe- but more strongly to severity. Damage was not significantly related to disease ty of methotrexate (MTX) in rheumatoid arthritis (RA) patients. duration (r=0.046, p=0.263), but correlated with peripheral vascular involve- Methods The search was performed in Medline, Cochrane, Embase and ment (r=0.195, p<0.001), joint/tendon involvement (r=0.252, p<0.001), mus- has been extended with a hand search, and ACR and EULAR abstracts of cle involvement (r=0.259, p<0.001), skin involvement (r=0.477, p<0.001), the 2 last years. The population studied were adult RA patients who gastrointestinal tract involvement (r=0.154, p<0.001), heart involvement received MTX monotherapy for at least two years. The data collected were (r=0.326, p<0.001) and kidney involvement (r=0.271, p<0.001). incidence rate, risk ratio, odd ratio or standardized incidence rate (SIR) Conclusion We conclude that the CSRG has more real world database of SSc concerning mortality, cardiovascular diseases (CVD), malignancies, liver with low average activity, damage and severity scores and data tend to be toxicity, infections, other adverses events and percentages of withdrawals skewed to low scores. However, this is the first data to determine the rela- for toxicity. tionships between activity, severity and damage in SSc and this is important Results Using combinations of key-words, we obtained 2,449 articles. On for future outcomes research. titles and abstracts, 2,269 were excluded. The remaining 180 publications were reviewed. Finally, 88 published studies and 8 congress abstracts were 77 included. Concerning mortality and comparability to the general popula- An Innovative Approach to Practice Based Post-marketing Surveillance tion, RA patients receiving MTX have an increased risk of death. But in of Rheumatoid Arthritis Using an Established Patient Surveillance comparison with RA-without MTX population, this drug seems to provide System: Results of a Feasibility Study a survival benefit by reducing cardiovascular mortality (Hazard ratio=0.3, Claire Bombardier (University Health Network, Toronto, ON), Ileana Ciurea 95% Confidence Interval: 0.2-0.7). This result is confirmed by two case (Canadian MedicAlert Foundation, Toronto, ON.), Janine English controls studies dealing with CVD, wherein MTX does not appear as a risk (University Health Network, Toronto, ON), Annette Wilkins (University factor of CVD in RA patients and could reduce this risk: OR = 0.11 (95% Health Network, Toronto, ON) CI 0.02- 0.56). Compared to other DMARDs based on toxicity index Objective To test the Canadian MedicAlert Foundation data collection oper- scores, MTX appears to be more toxic than hydroxychloroquine (HCQ) ations as a method for collecting specific clinical data that can be used for and Gold and less toxic than Auranofin. Nevertheless, during long term prospective disease surveillance. therapy (from 5 to 10 years), the termination rate of MTX for toxicity is Methods MedicAlert consulted key rheumatology opinion leaders within less than Gold, D-penicillamine and close to HCQ. The data on liver toxi- Ontario to conduct a quality assessment of their existing procedures to deter- city are conflicting: a meta-analysis shows an incidence of fibrosis of 3% mine its potential role in disease surveillance. Key items relating to long-term after 4 years of MTX .However, three studies on sequential liver biopsies patient surveillance included sustainability of infrastructure, incentive for do not show evidence of progression of histological grade or fibrosis, patients to participate, and inclusion of marginalized patient population (e.g. whereas few patients show some progression in two other reports. those with a language barrier). The MedicAlert database houses member Regarding the elevation of liver enzymes, pooled results of 27 prospective records that are updated passively by either members via the secured studies show a prevalence of 13% (elevation > 2 upper limit of normal) and MedicAlert website or by trained MedicAlert customer service representa- of 5% for permanent discontinuation due to liver toxicity. MTX use was no tives. This database is hosted at a secured data centre with 24/7 monitoring risk factor for infections, serious infections, herpes zoster and post-surgery and enhanced security features that meet RCMP, Communications Security infections. For lymphoma, results of observational studies are inconclusive Establishment, and government standards. For all members who indicated mainly because risk estimates were based on the general population as ref- rheumatoid arthritis (RA) as a medical condition, demographic variables, erence. DMARD and biologic drug use, and comorbidities were reported. A strati- Conclusion This systematic literature search on MTX use during at least 2 fied sample of these members were contacted to a) update their record, b) years shows a favourable long-term safety. screen eligibility to participate in the feasibility study (4 questions) and c)

Downloaded on September 27, 2021 from www.jrheum.org schedule the telephone administration of the RA questionnaire by a trained 79 MedicAlert interviewer. The questionnaire contained 23 clinical questions Gender and Autoantibodies in Systemic Sclerosis (including the HAQ, RADAI, global assessment of disease, arthritis medica- Marie Hudson (McGill), Brett Thombs (McGill), Marvin Fritzler (University tions and comorbid conditions), 9 socio-demographic questions and eight of Calgary), Jessica Bernstein (Jewish General Hospital), Murray Baron questions regarding the appropriateness of MedicAlert as an interview serv- (Jewish General Hospital) ice and data custodian. Objective Sex hormones are known to influence humoral immunity. We Results A total of 149 of the 178 (83.7%) members deemed eligible for this undertook this study to determine whether gender is related to the expression study agreed to participate and 135 completed the study questionnaire. of autoantibodies in systemic sclerosis (SSc). Participants were mostly female (76.3%) with an average age of 64 years. The Methods Patients in the Canadian Scleroderma Research Group registry average duration of administration for the arthritis questionnaire was 30 min- underwent a standardized assessment, including history and physical exami- utes and four minutes for the patient feedback questionnaire. Only 3% of par- nation. Anti-centromere antibodies were assayed by screening indirect ticipants reported difficulty in understanding the questionnaire, 85.2% felt immunofluorescence on HEp-2 cells and confirmed by a line assay (InnoLIA, that the length of the questionnaire was appropriate and 94.1% felt that the Innogenetics) and anti-topoisomerase (topo I, Scl-70) antibodies were level of detail was appropriate for addressing the various aspects of living assayed by an addressable laser bead immunoassay (QuantaPlex 8, Inova, San with RA. 98.5% of participants reported that they would trust MedicAlert to Diego, USA). Demographic, clinical and serological differences between men collect and safeguard their data through a program that would monitor patient and women were compared using t tests and chi square tests. Logistic regres- outcomes through interviews such as the one piloted during this study. sion was undertaken to determine the association between gender and anti- Conclusion Initial assessment of this system using participants recruited from body profiles, adjusting for disease duration and diffuse versus limited status. the member database indicates that there is an infrastructure and capability Results This study included 530 patients (477 women and 72 men). Disease that would allow for prospective disease surveillance using the MedicAlert duration was significantly longer in women than in men (14 versus 11 years, system. These results indicate that this approach to post-marketing surveil- p = .02) and a greater percentage of men had diffuse disease compared to lance warrants further study. women (54% versus 39%, p = .03). Anti-centromere antibodies were more common in women than in men (27% versus 7%, p = .02) and anti-topo I anti- 78 bodies were more common in men than in women (33% versus 18%, p = .01). Characteristics of Patients with Rheumatoid Arthritis Who Are In logistic regression analysis adjusting for disease duration and diffuse ver- Members of the MedicAlert System in Ontario sus limited status, women were 2.5 times more likely than men to have anti- Claire Bombardier (University Health Network, Toronto, ON), Ileana Ciurea centromere antibodies (95% confidence interval 1.1-5.7, p = .04) and men (Canadian MedicAlert Foundation, Toronto, ON.), Janine English (University were 2.2 times more likely than women to have anti-topo I antibodies (95% Health Network, Toronto, ON), Annette Wilkins (University Health Network, confidence interval 1.1- 4.3, p = .02). Toronto, ON) Conclusion This study establishes that there are baseline differences in Objective To describe the context of the current MedicAlert member database autoantibody profiles between men and women in a large Canadian cohort of and to present data on their existing rheumatoid arthritis (RA) member popu- patients with SSc. The data provide new insight into the role of sex hormones lation within Ontario. and auto-antibodies in the etiopathogenesis of this disease. Methods MedicAlert consulted key rheumatology opinion leaders within Ontario to conduct a quality assessment of their existing database to deter- 80 mine its potential role in disease surveillance. For all patients who indicat- Folic Acid and Folinic Acid for Reducing Side Effects in Patients ed RA as a medical condition in their member profile, demographic vari- Receiving Methotrexate for Rheumatoid Arthritis (A Systematic Review ables, DMARD and Biologic use, and comorbidities were reported. As and Metaanalysis) well, geographic distributions of these members were determined via post- Wanruchada Katchamart (University of Toronto, ON), Zulma Ortiz (National code. All MedicAlert member records were de-identified for personal Academy of Medicine, Beunos Aires, Argentina), Beverley Shea (Loeb information. Health Research Institute, University of Ottawa, ON), Peter Tugwell Results The MedicAlert database stores member records that are updated pas- (Department of Medicine, University of Ottawa, ON), Claire Bombardier sively by either members via the secured MedicAlert website or by trained (University Health Network, ON) MedicAlert customer service representatives. This database is hosted at a Objective To assess the effects of folic acid and folinic acid in reducing the secured data centre with 24/7 monitoring and enhanced security features mucosal and gastrointestinal (GI), liver and haematologic side effects of low- that meet RCMP, Communications Security Establishment (CES), and gov- dose of Methotrexate (MTX) in patients with Rheumatoid Arthritis (RA) and ernment standards. A total of 2561 member records indicated RA as a med- to determine whether or not folate supplementation alters MTX efficacy. ical condition of which 80.5% (n=2061) were female and 59.4% (n=1520) Methods Search strategy: We searched the Cochrane Controlled Clinical were >65years old. DMARD use was reported in 43.0% (n=1102) with Trial’s Register (CCTR), Medline and Embase up to and including July 2007 methotrexate (64.4%) and hydroxycholoroquine (39.7%) accounting for the and bibliographic references of the relevant review. All languages were most commonly used DMARDs. Currently only 5.1% (n=131) of members included. reported using a biologic response modifier (BRM) with etanercept repre- Selection criteria: We selected all double-blind, randomized, placebo-consenting 60.3% of overall use. Comorbidities identified within this cohort trolled, clinical trials (RCTs), in which adult RA patients were treated with a include hypertension (30.9%) and diabetes (25.4%). Myocardial infarcts low dose of MTX (equal or less than 25 mg / week) concurrently with folate were identified in 5.9% of members with RA. Most members (79.1%, supplementation. n=2027) were shown to reside within an urban setting with the geographic Data collection & analysis: Three observers extracted the data and assessed distribution situating 44.7% of members in Central Ontario, 22.3% in the quality of the trials. (BS, Z0, WK) The overall treatment effect across tri- Eastern Ontario, 21.2% in Southwestern Ontario and 11.8% in Northern als was calculated using a fixed effect model. Subgroup analyses were con- Ontario. ducted evaluating different doses and sensitivity analysis looking at the qual- Conclusion The MedicAlert member database is housed in a highly secured ity of the trials. Heterogeneity of the trials was measured using a standard chi environment to maintain the confidentiality of its members. Their RA mem- square test and I2 test. ber population in the context of age, gender and drug usage is indicative of Results Nine studies with 793 patients met the inclusion criteria. Two-hun- what is observed in clinical practice and clinical trials. As well, the member dred and twenty two (221) patients were treated with folinic acid and 238 profile demonstrates that MedicAlert has a geographically representative patients with folic acid. For folic acid, only high dose (more than 5 mg/wk) sample of RA patients throughout Ontario. reduced the risk of GI side effects and liver toxicity significantly [OR = 0.42

Downloaded on September 27, 2021 from www.jrheum.org (95%CI 0.21 to 0.85), OR = 0.17 (95%CI 0.09 to 0.32) respectively ]. There Objective Systemic sclerosis (SSc) is a serious, chronic, multisystem disease were no data available for liver toxicity in the low dose folic acid. For folinic that has been reported to be associated with impaired health-related quality of acid, only low dose folinic acid (equal or less than 5 mg/wk) decreased risk life (HRQoL). However, studies that have investigated HRQoL in SSc have, of GI side effects and liver toxicity significantly [OR=0.39 (95%CI 0.2 to in general, had small samples and variable results. To gain greater insight into 0.76), OR = 0.16 (95% CI 0.09 to 0.29) respectively]. Folic acid and low dose the HRQoL of patients with SSc, we undertook a systematic review of the lit- folinic acid did not interfere with disease activity while high dose folinic acid erature in which HRQoL was measured using the Medical Outcomes Trust showed an increase in the number of tender and swollen joint significantly Short Form 36 (SF 36). [OR=6.27, 95%CI 1.64 to10.90 and OR=5.3(95%CI 0.03 to10.58) Methods A comprehensive search was conducted in July and August 2007 respectively]. using Medline, CINAHL and Embase to identify original research studies Conclusion The results support the protective effect of folate supplementa- reporting SF 36 scores of patients with SSc. The search was augmented by tion in reducing MTX side effects related to the liver and GI systems but only reviewing references from selected studies and recent review articles. Selected studies that used low dose MTX. We could not determine if folic acid was dif- studies were reviewed by two independent investigators using a pre-determined ferent from folinic acid. data abstraction form working by consensus. When duplicates of data occurred, the most complete data set or the article whose focus was more specifically on 81 HRQoL in SSc was retained. Characteristics of the study samples, including The Efficacy and Toxicity of Methotrexate Combination vs. numbers with limited and diffuse disease and SF 36 data, including subscale Monotherapy in Rheumatoid Arthritis: An Updated Systematic Review and/or summary scores, was extracted. Corresponding authors of selected stud- and Metaanalysis ies were contacted for supplemental information when these data were incom- Wanruchada Katchamart (University of Toronto, ON), Claire Bombardier plete in the original papers. SF 36 physical and mental component summary (University Health Network, ON) scores (PCS and MCS, respectively) are normalized at 50 and scores below and Objective To evaluate the efficacy and toxicity of Methotrexate (MTX) com- above 50 indicate worse and better HRQoL, respectively. bination therapy compared with MTX monotherapy in rheumatoid arthritis Results Twelve datasets with a total of 1046 SSc patients were included in the patients. systematic review. Results from these showed that HRQoL was impaired in Methods The following bibliographic databases including Medline (1950 to SSc, with SF 36 PCS scores ranging from 33.4 to 43.8 and SF 36 MCS scores June 2007), Embase (1980 to 2007 Week 25) and Cochrane Central Register from 41.0 to 50.7. In some, but not all studies, SSc patients with diffuse dis- of Controlled Trials (CCRT)(2nd Quarter 2007)were searched. References ease had worse SF 36 scores than those with limited disease. lists of relevant reviews from the electronic search were manually searched to Conclusion HRQoL in SSc, when measured using the SF 36, is impaired. identify additional eligible trials. All languages were included. Eligible stud- Although the impairment appears greater in physical health, mental health ies were randomized controlled trial comparing between MTX combination impairment is also reported. Further research is needed to determine whether and MTX alone. Outcomes of interest were clinical and laboratory response, HRQoL is significantly different in limited and diffuse SSc. radiographic progression and reports on toxicity. We used RevMan 4.2.10 for analysis. The results of efficacy were stratified into three strategies, MTX 83 naïve, parallel treatment (MTX-N), MTX failed, step-up treatment (MTX-F) The Response of Scleroderma Associated Pulmonary Arterial and non-MTX failure, step-up treatment (Non-MTX-F). The end of trial Hypertension (SSc-PAH) Is Not Worse Than in Idiopathic Pulmonary results of dichotomous data were pooled and estimated using the Peto odd Hypertension (iPAH): Analysis of a RCT and OLE of Sitaxsentan ratio. The heterogeneity of the trials for each pooled analysis was estimated Janet Pope (University of Western Ontario, London, ON), Sanjay Mehta using the chi-square test and I2 test. Fixed effects models were used through- (University of Western Ontario, London, ON) out. Objective Pulmonary arterial hypertension (PAH) is a leading cause of death Results Twenty studies with 1827 patients were included. MTX combination in scleroderma (SSc). SSc associated PAH is regarded as less responsive to therapy was more effective than MTX monotherapy significantly in MTX-N, treatment than idiopathic PAH (iPAH). Endothelin (ET) levels are increased with OR 2.24 (95%CI 1.41-3.56), 2.31 (95%CI 1.25-4.27) and OR 3.38(1.17- in SSc-PAH. Sitaxsentan is a once daily, oral, highly selective (6500:1 - A:B) 9.77) for ACR 20, 50 and 70 response respectively and in MTX-F with OR ETA receptor antagonist (ETRA). ETRAs have been shown to be effective in 3.78 (95%CI 2.66-5.37), OR 4.59 (95%CI 2.73-7.71) and OR 4.76 (95%CI iPAH and in SSc-PAH but SSc patients are older and may not do as well with 2.31-9.83) for ACR 20, 50 and 70 response respectively. For non-MTX-F, a high mortality in SSc-PAH. The objective was to determine the proportion data from only one study of 110 patients showed a trend favouring MTX com- of patients with SSc-PAH who responded to long-term treatment (change in bination therapy but it was not significant. When evaluating the number of WHO functional class [FC]) with sitaxsentan compared to iPAH. patients who withdrew due to lack of efficacy, combination therapy had less Methods STRIDE-2 was a randomized, placebo-controlled, 18 week, multi- patient withdrawal than monotherapy in the MTX-N and MTX-F groups sig- center study in PAH (FC I-IV). 245 were randomized to: sitaxsentan 50mg nificantly with OR 0.38 (95%CI 0.18-0.8) and 0.39(95%CI 0.2-0.75) respec- daily, sitaxsentan 100mg daily, bosentan 125mg BID, or placebo. At 18 tively. For the patients who failed non-MTX DMARDS, there was no differ- weeks, patients continued in the open label STRIDE-2X study. Patients on ence between MTX mono- and combo- therapy. Combination therapy result- sitaxsentan 100mg daily or bosentan 125mg BID were continued. Placebo ed in more withdrawal due to adverse reactions than monotherapy in only were randomized to sitaxsentan 100mg daily or bosentan BID and patients combination of MTX+ Cyclosporin and MTX+ Azathioprine with OR of receiving sitaxsentan 50mg were increased to 100mg daily. 2.03, 95%CI 1.06-3.88) and OR of 4.69 (95%CI 1.78 -12.32) respectively. Results 145 patients in STRIDE-2X received sitaxsentan 100mg daily. Most MTX+Azathioprine and MTX+ intramuscular gold increased the risk of total were women of whom 89 (61%) had iPAH, and 42 (29%) had CTD-PAH (SSc side effects with OR 3.65 (95%CI 1.67-7.98) and OR 4.19 (95%CI 1.56- 29; overlap 19; SLE 5). SSc were older than iPAH (mean age: 64 vs 56 years). 11.86) respectively. Baseline 6MWD was 322+88 (SD) in SSc compared with 355±74 in iPAH. Conclusion MTX combination therapy is more effective than MTX More patients with iPAH were FC III (60%) compared to SSc (48%) at base- monotherapy especially in patients who never received or failed MTX. line; FC II in SSc was 45% vs iPAH 36%. Overall, 77% of SSc and iPAH Toxicity varied depending on the regimen. completed 1 year on monotherapy sitaxsentan. At study end, 90% of SSc improved at least one FC (28%) or remained unchanged (62%), whereas 91% 82 of the iPAH improved at least one FC (21%) or remained unchanged (70%). HRQoL in SSc Worsening in FC at week 52 (vs. baseline) occurred in 10% of SSc, and 9% Marie Hudson (McGill), Brett Thombs (McGill), Russell Steele (McGill), of iPAH. Sitaxsentan was well tolerated, with 1 patient discontinuing with Evan Newton (McGill), Murray Baron (McGill) transaminitis.

Downloaded on September 27, 2021 from www.jrheum.org Conclusion The response was similar between SSc-PAH and iPAH, but SSc Methods This prospective observational study was designed to investigate the started with a worse baseline 6MWD and thus were likely sicker despite clinical course, treatment patterns and outcomes of early RA patients across slightly more in FC II at baseline. This may be contrary to what was expect- Canada and the United States. Early RA was defined as having signs and ed. Sitaxsentan was well tolerated and effective in SSc-PAH. However, SSc- symptoms of RA, as determined by a board-certified rheumatologist for > PAH may do better if detected early, so a high awareness from rheumatolo- 3months but <12 months. Data were collected from physicians annually and gists is paramount. from patients every 4 months for a duration of 3 years. A total of 806 patients were available for this analysis with baseline and 1 year complete follow-up. 84 All variables were compared as continuous using the Pearson correlation A Qualitative Study to Determine Best Methods for Post-marketing coefficient. Furthermore, ten patient groups were created and the deciles of Surveillance in Usual Rheumatology Care in Ontario patients were ranked from the lowest to highest DAS28-CRP score, SDAI and Claire Bombardier (University Health Network, Toronto, ON), Janine CDAI, respectively to assess agreements of different scores with weighted English (University Health Network, Toronto, ON), Carter Thorne (Southlake kappa analysis. Regional Health Centre, Newmarket, ON), Alf Cividino (St. Joseph’s Results At baseline, patients had a mean age of 52.7 years (SD 14.6; range Hospital, Hamilton, ON), Janet Pope (St. Joseph’s Health Care, London, 19, 86). Seventy-one percent of patients were female with a median disease ON), and the Ontario Biologics Research Initiative (University Health duration of 1.5 months (range 0, 12). Disease activity and health status param- Network, Toronto, ON) eters for these patients at baseline included the Health Assessment Objective To determine best methods for post-marketing surveillance (PMS) Questionnaire Disability Index (mean, 1.0, SD, 0.73), SF-36 Physical in usual rheumatology care in Ontario with an emphasis on low cost and sus- Component Summary (mean % score, 34.2), Rheumatoid Arthritis Disease tainable procedures. Activity Index (mean 4.5, SD 1.9), and DAS28-CRP (mean, 5.0 SD 1.4), Methods Key informant interviews were conducted with 14 Ontario rheuma- SDAI (mean 32.3, SD 17.8), and CDAI (mean 28.4, SD 15.9). Pearson corre- tologists (10% of total) who commonly treat rheumatoid arthritis (RA) and lation of DAS28-CRP was 0.50, 0.95, and 0.91 with HAQ, SDAI, and CDAI, who represent a range of practice styles including solo/group, academic/com- respectively. There were very good agreements of the DAS28-CRP with the munity, rural/urban and other characteristics. Interviews consisted of open SDAI and CDAI (k=0.85 and 0.76, respectively). At 1-year follow-up, the ended questions regarding current data collection methods currently used, DAS28-CRP, SDAI and CDAI significantly decreased 1.0, 10.7 and 10.3, ability to collect informed consent, patient recruitment issues, financial sup- respectively (p<0.001). port and other incentives to facilitate PMS as a low cost and sustainable com- Conclusion This large North American cohort represents a vast population of ponent of usual care. Results were reviewed with a subgroup of rheumatolo- early RA patients with high disease activity at baseline. Significant improve- gist-participants to confirm interpretations and develop final recom- ments were observed in the DAS28-CRP, SDAI and CDAI at one year of fol- mendations. low-up. All findings of the study showed the excellent correlation between Results Most participants felt that using paper versus electronic Case Report DAS28-CRP with SDAI and CDAI in routine practice with consistent Forms (CRFs) was the most comfortable for their office environment. While changes over time. As the SDAI or CDAI are more feasible instruments in all sites had access to a fax machine, not all sites had an internet connection. clinical practice, employing them as assessment strategies and modifying Most participants see RA patients at least twice a year therefore a biannual therapy accordingly, will help improve disease outcomes in the future. patient assessment would be acceptable. Participants currently use a wide range of data collection forms including standardized questionnaires (e.g. 86 HAQ). It was agreed that PMS CRFs must be brief and straightforward but Learning from Past Mistakes: Assessing Trial Quality, Power and will probably not replace current charting techniques. All participants felt Eligibility in Non-Renal Systemic Lupus Erythematosus (SLE) comfortable in collecting informed consent. However, it was noted that a sec- Randomized Controlled Trials ond consent should be collected by program staff, despite cost, to ensure that Sai Yan Yuen (University of Western Ontario, London, ON), Janet Pope all patients have been consented fully in a standardized manner. The greatest (University of Western Ontario, London, ON) perceived barrier to patient recruitment was language. All participants felt Objective Systemic lupus erythematosus (SLE) is a relatively rare autoim- that full participation of the widest possible range of patients was vital to PMS mune disease, with various organ manifestations, so recruitment of a suffi- and warrants the cost of translation. Low cost incentives were discussed and cient sample size for randomized controlled trials (RCTs) can be difficult. those identified include the ability to use PMS activities for Continuing Also, stringent inclusion/exclusion criteria diminish the number of eligible Professional Development credits, feedback on patient and practice charac- patients. Type II or beta errors are frequent in medical literature when studies teristics, full assistance with ethics submissions and maintenance, and the are “underpowered”. The objective of this project was to evaluate the post ability to align the data collected through PMS with the requirements for hoc study power of (RCTs) in the treatment of non-renal disease in SLE and Individual Clinical Review, the publicly funded procedure for approval of bio- to determine the generalizability of these RCTs using a SLE database. logics and other therapies in Ontario. Methods RCTs related to SLE were identified using the Pubmed database Conclusion Recommendations for PMS in rheumatology care in Ontario from 1975 to 2007. Publications on SLE renal disease were excluded. include the use of paper CRFs with fax back to the data management centre, Inclusion and exclusion criteria, trial quality (5-point scale) and results of a brief clinical form to be completed biannually, methods to address the het- each study were recorded. The inclusion/exclusion criteria were used in con- erogeneity of the Ontario population (e.g. language), centralized consent and junction with a SLE database including ACR criteria, clinical manifestations, provision of a range of low cost incentives that rheumatologists can chose SLAM, SLEDAI and SLICC to determine the proportion of SLE patients who from to best fit their needs. would theoretically be eligible for these trials. For each study that reported a non-significant difference in the primary outcome, we calculated the post hoc 85 study power. If the primary outcomes were not explicitly reported, the most Correlations of Disease Activity Score (DAS) 28-C-Reactive Protein with clinically relevant outcome measure was considered. Only RCTs with 2 the Simplified Disease Activity Index (SDAI) and the Clinical Activity groups and sufficient outcome data were included in this analysis. We looked Disease Index (CDAI) in an Inception Cohort with Early RA for temporal improvements of study trials in the literature. We also deter- Xiuying Li (University Health Network), Claire Bombardier (University mined if pharmaceutical involvement influenced trial quality. Health Network) Results In total, 64 articles were included; the mean power of 30 negative Objective To describe the disease activity in an inception cohort with early studies was 24.6% ± SEM 3.9% (ranges 2.5% to 81.1%). In the negative rheumatoid arthritis (RA) and estimate the correlations between DAS 28- studies, only one had a study power >80%. Overall potential eligibility of CRP, SDAI and CDAI. patients with SLE in a database was 45.1% ± SEM 3.6%. The mean score for

Downloaded on September 27, 2021 from www.jrheum.org trial quality was 2.4/5. Only 14 studies (21.9%) had good quality. Fortunately, Methods This study was a retrospective chart review of gout patients seen in in non-renal lupus RCTs quality is improving over time (trials <1995, com- the outpatient rheumatology clinic at Sunnybrook HSC. Subjects were identi- pared to 1996-2002 and >2003; p<0.001). Trials with pharmaceutical involve- fied by the OHIP billing code for gout. Based on guidelines from EULAR and ment had a significantly higher number of enrollees with a trend for a better Mikuls, an audit tool was created for this study to gather information on basic study quality. demographics, risk factors and symptoms of gout, treatment strategies and Conclusion Negative RCTs in the treatment of SLE were mostly underpow- outcomes. Data was analyzed to assess the frequency of risk factors and clin- ered but the generalizability of these trials was high so recruitment should not ical parameters of gout patients treated at SHSC. The results were then com- have been a deterrent to performing the trial. Determination of study power pared to published recommendations to evaluate the quality of care provided. and impact of eligibility criteria on generalizability of study results are need- Results 103 charts were reviewed. The mean age of the patients was 63.1 (27- ed in the design of clinical trials, so we can advance proven treatment in non- 93) and 85.4% were male. Visit dates ranged from January 1996 to July 2007. renal manifestations of SLE. 11 patients (10.7%) were obesity. 59 patients (57.3%) had hypertension. 13 patients (12.6%) had nephrolithiasis. 20 patients (19.4%) had renal impair- 87 ment. 27 patients (26.2%) consumed more than one drink of alcohol a day. 6 A Case of Rapid Multisystem Failure with Systemic Sclerosis patients (5.8%) were hyperglycemic. 9 patients (8.7%) had poor long term Kasia Czarnecka (University of Toronto), Shahin Jamal (University of sugar control. The mean of serum uric acid level was 439.7 µmol/L (162 to Toronto) 876 µmol/L). The mean triglyercide level was 2.18 mmol/L (0.71 to 4.31 Objective To describe a case of rapidly progressive multi-system failure in a mmol/L). Patients received counseling on appropriate lifestyle issues to a patient with new onset systemic sclerosis (SSc). varying degree (weight loss 18%, diet modification 57%, alcohol reduction Methods A retrospective chart review was performed and the case described. 74%). 92% of patients without significant renal impairment and peptic ulcer Results A 57-year old male was admitted to hospital with a 6 month history disease were treated with NSAIDS, colchicine or prednisone. 81.1% of of 60 lb weight loss, skin tightening over face, thorax, arms and feet, patients with severe gout were treated with urate-lowering therapy. Colchicine Rayaud’s phenomenon, periungal erythema, splinter hemorrhages, bowel dys- daily was the preferred choice for prophylactic suppression when initiating motility, muscle weakness and dyspnea. Anti-SCL70 and anti-centromere urate-lowering therapy. Despite treatment, 40% of patients in this group are antibodies were negative. Pulmonary function tests showed restrictive lung still experiencing acute gouty attacks or chronic tophaceous gout. disease. Interstitial fibrosis was confirmed by CT thorax and lung biopsy. Conclusion Demographic data from this cohort supports risk factors previ- MRI and muscle biopsy found rhabdomyalysis without inflammatory muscle ously reported in the literature. Even before the publication of recent guide- disease. Endoscopy revealed non-specific diffuse bowel thickening. lines, Sunnybrook rheumatologists had already been managing gout with Echocardiogram showed normal cardiac structure and function without pul- strategies closely matched to such recommendations; thus showing that they monary arterial hypertension (PAH). Cardiac catheterization was normal. can be easily applied to everyday clinical practice. These results will serve as The patient was diagnosed with diffuse systemic sclerosis and treated with a basis for future prospective studies and for a survey of local rheumatologists high dose corticosteroids for pulmonary disease. Over a two-week course in regarding the published recommendations. hospital, the patient’s health status rapidly deteriorated despite treatment. He developed respiratory failure requiring intubation, acute renal failure requir- 89 ing dialysis, liver failure and rising troponin to 8.0, complicated by intermit- Oncogenic Osteomalacia. A Case Report and Literature Review tent atrial and ventricular fibrillation. Repeat echocardiogram showed global Azar Bahrami (McMaster University), Derek A. Haaland (McMaster left ventricular hypokinesis, severe right ventricular dilatation, and right ven- University), David N. Churchill (McMaster University), Kenneth P.H. tricular systolic pressure of 58 mmHg. Cardiac caheterization found a mean Pritzker (University of Toronto), J.D. Adachi (McMaster University) pulmonary artery pressure of 40 mmHg, systemic vascular resistence was Objective and Methods Presentation and discussion of a case of oncogenic >1200 with a cardiac index of 2.0. Work-up for infection was negative. osteomalacia. Despite pressure support, intubation, and dialysis, the patient died. Autopsy Results A previously healthy 37-year-old male with no significant past med- was declined. This syndrome of rapidly progressive multi-system failure in ical history was referred for assessment of pain and muscle weakness. He had systemic sclerosis has not been well described in the literature. In this case, we a three-year history of pain in his feet and ankles, which had progressed to suspect that his rapid deterioration was primarily due to cardiomyopathy with involve the legs and ribs. He also complained of proximal muscle weakness, myocardial fibrosis and immune mediated myocarditis. This is supported by a progressive to the point that he had difficulty dressing himself. Medications rapidly rising troponin in the setting of normal coronary arteries and progres- included risedronate 30 mg daily plus ibuprofen and methocarbamol on an as sive biventricular cardiomyopathy with mild pulmonary hypertension. The lit- needed basis. Family history was noncontributory. Positive findings on phys- erature reports over 80% prevalence of myocardial involvement in SSc, rang- ical examination included proximal muscle weakness in the lower extremities ing from diffuse biventricular myocardial fibrosis to contraction band necrosis. with a positive Gowers’ sign and a waddling gait. Laboratory investigations A correlation has been shown with skin and visceral involvement. revealed low serum phosphate at 0.51 mmol/L (0.80-1.45), normal calcium at Conclusion We describe a case of rapidly progressive cardiac, pulmonary and 2.27 mmol/L (2.10-2.55), albumin 44 g/L (35-50), high alkaline phosphatase renal failure in a patient with new onset systemic sclerosis. This case may rep- at 244 U/L (40-120). Serum 1, 25 dihydroxy vitamin D was low normal at 54 resent an uncommon subset of SSc who develop rapidly progressive multi- pmol/L (30-120) and parathyroid hormone was 32 pg/mL (8-50). 24-hour system failure. Recognition of such a subset of patients is necessary to better urine collection showed high urine phosphate at 48 mmol/dL (11-42) with counsel patients, families and other health care professionals. normal creatinine 17.6 mmol/dL (7.0-18.0) and calcium 4.7 mmol/dL (2.5- 7.5). Bone mineral density revealed low bone mass with T scores of -3.5 and 88 -2.5 at the femoral neck and lumbar spine, respectively. Imaging revealed Gout: A Review of Quality of Care in Current Practice Looser zones in the femoral necks and sacral alae bilaterally. A diagnosis of Mary Bell (Sunnybrook HSC, University of Toronto), Gregory Choy hypophosphataemic osteomalacia was made and treatment with phosphate (Sunnybrook HSC, University of Toronto), Greg Dodge (Sunnybrook HSC, two grams daily and vitamin D 50 000 international units twice weekly was University of Toronto), Roderick Cheung initiated, and the risedronate was discontinued. Persistent hypophosphataemia Objective 1. Assess the prevalence of risk factors in gout patients from the prompted consideration of oncogenic osteomalacia. Thus octreotide scintig- outpatient population at Sunnybrook HSC. 2. Audit clinical practice in the raphy and serum fibrosing growth factor (FGF) 23 (a phosphaturic hormone) management of gout patients of our community using these published quali- were ordered. Bone biopsy of the right iliac crest post tetracycline labelling ty indicators as guidelines. 3. Determine the clinical outcomes of gout revealed advanced osteomalacia with unmineralized osteoid. FGF 23 level patients at Sunnybrook HSC. was elevated at 192 RU/ml (normal < 180). Octreotide scan revealed accu-

Downloaded on September 27, 2021 from www.jrheum.org mulation in the right inguinal region and magnetic resonance imaging con- setting of a second study designed to assess the use of daily evaluation forms firmed a small nonspecific soft tissue mass just anterior to the inferior margin in ambulatory Rheumatology clinics, internal medicine residents at the of the right acetabulum within the joint capsule. Surgical resection of the University of Ottawa were asked to report the number of procedures per- tumour resulted in rapid improvement of the serum phosphate and total reso- formed. All residents rotating on Rheumatology were strongly encouraged to lution of the muscle weakness within six months. Pathology revealed a giant provide the form to their preceptor at the end of each clinic and document the cell tumour of soft tissue with clear margins. The differential diagnosis, inves- number and nature of procedures performed. tigation and treatment of oncogenic osteomalacia are discussed. Results In the background of the OSCE, 90% of residents surveyed have per- Conclusion Oncogenic osteomalacia is a rare paraneoplastic disorder that formed all of the procedures required at least once with the exception of the should be considered in patients presenting with pain, weakness, and low knee joint aspiration where only 63% had done so. The mean confidence level serum phosphate. for the procedures ranged from 2.21 to 3.87. The lowest levels were noted for knee aspiration (2.21), intubation (2.68) and bone marrow aspiration (2.89), 90 which were significantly (p<0.05) lower compared to other procedures. Self- Osteoporosis Prophylaxis in Rheumatoid Arthritis Patients reported formal training was lowest for the knee and bone marrow aspirations Stephanie Garner (University of Calgary), Michel Zummer (Universite de with 13/36 and 5/36 residents never having received any formal training. Montreal), Gilles Boire (Universite de Sherbrooke), Sharon LeClercq Twenty-two internal medicine residents completed a 1-month rotation on (University of Calgary), Vivian Bykerk (University of Toronto), Gunner Rheumatology. Seven faculty members completed a total of 210 daily evalu- Kraag (University of Ottawa), Janet Markland (University of Saskatchewan), ation forms. The number of evaluation forms ranged from 4 to 17 (mean 9.35) Diane Thomas (University of Alberta), John Thomson (University of Ottawa), per resident. An unexpected finding in this second study was that residents Jamie Henderson (University of New Brunswick), Steven Edworthy rotating on rheumatology reported performing a rheumatologic procedure in (University of Calgary) only 10.5% of clinics. Objective To review the glucocorticoid-induced osteoporosis(GIOP)prophy- Conclusion Residents report less formal training and lack confidence in the laxis practice patterns of Canadian rheumatologists treating people with knee aspiration compared to other procedural skills. They also perform rheumatoid arthritis. rheumatologic procedures infrequently during ambulatory Rheumatology Methods Members of the Canadian Rheumatology Association (CRA) were clinics. These findings may have important implications for curriculum invited to participate by the Canadian Rheumatology Association in a practice design. audit entitled «The Assessment in Rheumatology» (AIR) program. 65 Rheumatologists participated. Demographic and treatment information was 92 collected on PDAs for 1596 consecutive RA patients seen in regular clinics Resident Evaluations: The Use of Evaluation Cards in Rheumatology and aggregated, without personal identifiers, for analysis. Those patients tak- Ambulatory Care ing oral corticosteroids were identified from the total population. Patients Susan Humphrey-Murto (University of Ottawa), Nader Khalidi (McMaster treated with prednisone less than 5 mg/day, tapering doses, or intra-articular University), Lori Albert (University of Toronto), C.D. Smith (University of or intramuscular steroids were excluded. Data was analyzed with the statisti- Ottawa), Heather Macdonald (University of Toronto), Timothy J. Wood cal software Stata. (University of Ottawa) Results Of the 1596 patients, 313 (19.6%) were taking a dose equal or greater Objective The in-training evaluation (ITER) is widely used to assess clinical than 5mg of prednisone a day. There were 226 patients on 5-10 mg /day, 40 skills, but has limited validity and reliability. Hence, alternate methods of on 11-25 mg/day and 7 on >25 mg/day. The mean age in this group of patients assessing clinical performance using multiple patient encounters and raters was 61.3 years (SD 14.0) with a range of 18-89. There were 222 (70.9%) have been developed. The purpose of this study was to assess the feasibility, females in the group, and 169 were over the age of 50 years. Rheumatologists validity, reliability and impact on feedback of using daily evaluation forms to had classified 54 (17.2%) patients as having osteoporosis. Osteoporosis med- evaluate residents in ambulatory rheumatology clinics at the University of ications included Bisphosphonates (n=158, 50.5%), Vitamin D (n=155, Ottawa and McMaster. 49.5%), Calcium (n=152, 48.6%), and Hormone Replacement Therapy Methods An evaluation form was developed based on the Royal College of (n=13, 4.2%). 81 (25.9%) patients were not taking any osteoporosis medica- Physicians and Surgeons of Canada Can MEDS roles. There were 12 evaluations. tion items (history, physical exam, clinical judgment, verbal communication, Conclusion Glucocorticoid-induced osteoporosis (GIOP) is a serious concern written records, humanistic qualities, collaborator, organization, scholar, advo- for rheumatoid arthritis patients. There is a significant care gap in GIOP pro- cate, procedural skills) including overall clinical competence. They were rated phylaxis in usual rheumatology practice. Methods for closing this gap require on a 5-point scale from unsatisfactory to outstanding. All internal medicine exploration. residents rotating on Rheumatology were strongly encouraged to provide the form to their preceptor at the end of each clinic. A questionnaire was developed 91 and collected before and after the implementation of the evaluation forms. Internal Medicine Residents Lack Confidence in Knee Aspiration Results Over an 18-month period of time, seventy- three internal medicine Susan Humphrey-Murto (University of Ottawa), Claire Touchie (University residents completed a 1-month rotation in Ottawa (n=26) and McMaster of Ottawa), Marty Friedlich (University of Ottawa), Timothy J. Wood (n=47). Faculty members completed a total of 637 evaluation forms. The (University of Ottawa ) number of evaluation forms ranged from 1 to 16 (mean 8.73) per resident. The Objective The Royal College of Physicians and Surgeons of Canada objec- average number of forms per resident in Ottawa was 10.46 and 7.76 at tives for Internal Medicine Certification require proficiency in: central venous McMaster. At an average of 8.73 forms per resident, the reliability was 0.87 catheter insertion, lumbar puncture, peripheral arterial catheter insertion, for the composite score. The composite score is the sum total of all categories abdominal paracentesis, endotracheal intubation, thoracentesis, knee joint on the evaluation form except the overall category. For the overall category, aspiration and electrocardiographic interpretation. The purpose of this study there was an average of 8.35 evaluation forms per resident collected and the was to assess resident training and confidence level in performing these pro- reliability was 0.54. In Ottawa, there was no impact on feedback noted, but cedures, with particular interest in the knee aspiration. 70.5% of the residents agreed or strongly agreed that the forms should con- Methods In the context of a formative OSCE in Internal Medicine at the tinue to be used. University of Ottawa held in February 2007, a total of 38 residents complet- Conclusion The use of daily evaluation forms is feasible and provides excel- ed a survey in which they were asked to self-report the number of specific lent reliability with 8-9 forms collected per resident over a 1-month period. procedures performed, their level of confidence in performing those proce- The forms were well received by faculty and residents and continue to be uti- dures (on a 5 point scale) and the formal training they had received. In the lized at both universities.

Downloaded on September 27, 2021 from www.jrheum.org 93 following in the areas of treatment strategies and biologic safety. Results of Certolizumab Pegol in Combination with Methotrexate Is Significantly the survey will be presented in greater detail. More Effective Than Methotrexate Alone in Patients with Active Rheumatoid Arthritis: Results from the Rapid 1 Study 95 Vivian Bykerk (U of Toronto), David Mason (United Belgium Chemicals, A Case of ANCA-Associated Vasculitis Induced by Both Propylthiouracil Atlanta), Edward Keystone (U of Toronto) and Methimazole Treatment for Hyperthyroidism Objective To investigate the efficacy and tolerability of two dose regimens of Mullein Thorleifson (University of Manitoba), Richard Lindenschmidt subcutaneous certolizumab pegol (CZP) as add-on therapy to methotrexate (University of Manitoba), David Robinson (University of Manitoba) (MTX) in patients with active RA who are refractory to MTX monotherapy. Objective Although ANCA-associated vasculitis (AAV) has been described Methods RAPID 1 was a phase III multicentre, double-blind, placebo-con- in association with propylthiouracil (PTU) and methimazole use for hyper- trolled, parallel-group 52-week study. Patients (previously treated for ≥6 thyroidism, we report a unique case of a single patient developing AAV in months with MTX) were randomized 2:2:1 to treatment with CZP (400 mg at association with both of these agents. Weeks 0, 2 and 4 followed by 200 or 400 mg every 2 weeks) plus MTX or Results A 59 year old woman with a history of Graves, managed on PTU pre- placebo plus MTX. Co-primary endpoints were ACR20 at Week 24 and sented with elevated acute phase reactants and neutropenia felt to be second- change in modified Total Sharp Score (mTSS) at Week 52. Secondary end- ary to PTU. Shortly afterwards she developed a vasculitic syndrome charac- points included the ACR50 and ACR70 responder rates. Efficacy and safety terized by palpable purpura, sinus headaches and a large mass on the nasal parameters were assessed at 2-week intervals. Patients who withdrew for any mucosa. Biopsies of the nasal lesion revealed necrotic material with an reason were considered non-responders. inflammatory exudate. Biopsy of the purpura revealed leukocytoclastic vas- Results 982 adult patients were randomized: CZP 200 mg, n=393; 400 mg, culitis. Her WBC was 2.1 x 106, ESR 82 mm/hr. There were no renal or pul- n=390; placebo, n=199. 572 patients completed the study (n=255, 274 and 43, monary manifestations. Methimazole was substituted at that time for the PTU respectively). At Week 24, ACR20 response was 58.8% in the CZP 200 mg because of leukopenia. No immunosuppresive medications were given. By group, 60.8% in the 400 mg group, and 13.6% in the placebo group (MTX three months later she had complete resolution of her nasal mass and pur- alone) (p<0.001 CZP vs placebo). ACR50 responses at Week 24 were 37.1% pura, and recovery of her WBC. Acute phase reactants at that time were nor- in the CZP 200 mg group, 39.9% in the 400 mg group, and 7.6% in the place- mal however her c-ANCA was positive with both anti-PR3 and anti-MPO bo group (p<0.001 CZP vs placebo). ACR70 response rates were 21.4% in positivity. Eight months after starting methimazole, she again developed pur- patients taking CZP 200 mg, 20.6% in those taking 400 mg, and 3.0% in puric lesions with increasing nasal symptoms. C-reactive protein was 55.9 patients taking MTX alone (p<0.001 CZP vs placebo). The proportion of and c-ANCA was positive with elevated titres of PR-3 and MPO. She received patients who experienced an adverse event (AE) was 74.7% and 76.6% in the radioactive iodine and methimazole was discontinued. Again no immunosup- CZP 200 mg and 400 mg groups, respectively, and 57.8% in the placebo pressives were given and there was resolution of her purpuric lesions. She has group. The majority of AEs were mild to moderate and discontinuation due to had no further vasculitis symptoms for one year following withdrawal of the AEs was low (4.3%, 5.7% and 1.5% in the CZP 200 mg, 400 mg and place- anti-thyroid medications. bo groups, respectively). Conclusion There are multiple reports of AAV occurring in association with Conclusion In MTX inadequate responders, CZP 200 mg every 2 weeks PTU as well as with methimazole. To our knowledge this is the first reported (after 3 initial doses of 400 mg) rapidly and significantly reduced the signs case of AAV occuring in association with both of these agents in a single and symptoms of active RA compared with MTX alone. The higher dose of patient. Simple withdrawal of each agent resulted in resolution of her vas- 400 mg every 2 weeks provided a similar benefit. Both doses were well tol- culitis symptoms. Clinicians should be aware of the association of either anti- erated, with a low incidence of discontinuation due to AEs. thyroid drug with AAV in order to avoid unnecessary immunosuppression in these patients. 94 Pre-guideline Survey on Pharmacological Treatment of Rheumatoid 96 Arthritis Simultaneous Development of Wegener’s Granulomatosis and Vivian Bykerk (University of Toronto), Carly Cheng (University of Toronto) Goodpasture’s Syndrome: A Case Presentation and Literature Review Objective The Steering Committee conducted a Canadian Rheumatology Sunita Mulpuru (University of Ottawa), Greg Knoll (University of Ottawa), Association Pre-guideline survey. The survey evaluated opinions on the phar- Claire Touchie (University of Ottawa), Sue Humphrey-Murto (University of macological treatment of rheumatoid arthritis in areas such as, treatment strat- Ottawa) egy and knowledge about infection. Based on the responses, more useful, Objective We present an interesting case of a patient diagnosed with C- focused and evidence based guidelines from the CRA will be provided for ANCA positive Wegener’s granulomatosis who subsequently developed renal application in clinical treatment. failure and was found to have Goodpasture’s syndrome. Our objective was to Methods All practicing rheumatologists in Canada were invited to participate determine if there is an association between the presence of anti-neutrophil (n=171) in a 33 question survey regarding the pharmacologic management of cytoplasm antibodies (ANCA) and anti-glomerular basement membrane anti- RA Physicians from across Canada participated; Ontario (43%), Quebec bodies (anti-GBM) in patients with vasculitis. Further, we aimed to identify (19%), Western Canada (30%), and Eastern Canada (8%). The majority of if this association may have prognostic and treatment implications for vas- rheumatologists practiced in an academic and/or teaching hospital setting culitis patients. (51%) and solo community practice (31%). Years of practice in rheumatology Method A 50-year-old woman presented with migratory arthralgias, recur- ranged from currently in a residency or fellowship program to greater than 30 rent epistaxis and hemoptysis. Physical examination was remarkable for years of experience with 26% having 10-20 years experience. 52% of rheuma- nasal mucosal ulcerations, splinter hemorrhages and palpable purpura of the tologists see patients where 25-50% of the patients have rheumatoid arthritis. lower extremities. Her urinalysis revealed blood and trace protein in context Results There is a good agreement in with the following: use of methotrex- of a normal creatinine (77 µmol/L). She was initially C-ANCA, anti-PR-3, ate, frequency of imaging, treatment strategies of a new patient with moder- and anti-GBM positive and a skin biopsy showed leukocytoclastic vasculitis. ate RA , the use of corticosteroids and decisions about switching biologic A CT scan of her thorax revealed changes consistent with pulmonary hemor- therapies. However there was variation in opinion in the areas of biologic rhage. Treatment included high dose solumedrol and cyclophosphamide. Her safety in regards to infection, malignancy, surgery, vaccination and screening symptoms resolved and fourteen days later she developed acute renal failure for TB. There were also knowledge gaps about the use of newer biologic (creatinine 170 µmol/L). A renal biopsy confirmed Goodpasture’s syndrome therapies. and she was treated with plasmapheresis resulting in mild renal improvement. Conclusion From these survey results, recommendations are required in the Results We reviewed the literature using the Medline search database to iden-

Downloaded on September 27, 2021 from www.jrheum.org tify articles documenting associations between ANCAs and anti-GBM anti- Granulomatosis (WG) manifested by Central Nervous System (CNS) involve- bodies. The nephrology literature reports that 5% of all ANCA positive ment, including Bell’s Palsy. We review the literature on the management of patients were also anti-GBM positive, while 32% of all anti-GBM positive CNS involvement in WG. samples also had detectable ANCAs. This may be clinically relevant as there WG is a chronic narcotising granulomatous small-vessel vasculitis that usual- are also reports of co-existent Wegener’s vasculitis and Goodpasture’s syn- ly presents with ear/nose/throat, pulmonary and/or renal involvement. drome. The temporal relationship of antibody development is unclear, how- Mononeuritis multiplex is the most frequent neurological involvement. CNS ever there has been a report of anti-GBM antibody formation following the involvement reportedly occurs in only 2% to 8% of patients. development of ANCAs. This has given support to the theory that ANCAs Our patient was diagnosed 2 years previously, with biopsy-proven renal cause renal damage which exposes antigens on the glomerular basement involvement, pulmonary nodules, mononeuritis multiplex and corneal ulcer- membrane resulting in the formation of anti-GBM antibodies. A recent study ation causing left eye blindness. Following induction of remission, mainte- demonstrated a worse prognosis for patients with both antibodies, especially nance was achieved with Methotrexate and low dose Prednisone therapy. when presenting with severe disease. She presented with a 3-day history of unsteady gait and vertigo, and new- Conclusion There is a documented association between the presence of onset left facial droop. Examination revealed horizontal and vertical nystag- ANCAs and anti-GBM antibodies in patients with vasculitis. Patients with mus and an ataxic gait. CT scan of her head was unremarkable. MRI Brain this dual antibody presence may have a tendency towards more severe renal demonstrated an intra-axial ovoid 1-centimetre mass suggestive of a granu- failure and worse clinical outcomes, especially when presenting with fulmi- loma on the right inferior cerebellar peduncle with surrounding edema and nant disease. In the context of ANCA associated vasculitis, physicians should swelling extending to the root entry zone of the facial nerve.. The patient consider measuring anti-GBM antibodies and treating co-existent was treated with pulsed intravenous Solumedrol (1 gram x 3 days), followed Goodpasture’s syndrome if necessary. by 1 mg/kg Prednisone and increased Methotrexate (20mg weekly). The facial palsy rapidly resolved and 3 weeks later the patient was ambulating 97 independently with the aid of a walker. Follow-up MRI reveals the response Impact of a Video on Learning the GALS Musculoskeletal Screening to therapy. Exam in Medical Students Conclusion CNS Granulomas are rare in WG and there is no accepted con- Joanna Bostwick (Medical Student McMaster University), Karen Beattie sensus on the treatment of these lesions. Our case demonstrates response to (Post Doctoral Fellow McMaster University), Alfred Cividino (Clinical high-dose pulsed intravenous steroids without the need for cyclophos- Professor McMaster University) phamide. Objective To assess the impact of a GALS musculoskeletal screening examination training video in medical students. 99 Methods A questionnaire was distributed to McMaster University’s School of Perceived Locus of Control and Coping as Major Factors Influencing Medicine Class of 2007 (N=130) after the OSCE exam in September 2005 Attainment of the Patient Acceptable State (PASS) in Patients with and April 2007. Students responded to six questions regarding their awareness Ankylosing Spondylitis of the GALS exam and whether they had reviewed the training video with a Walter Maksymowych (University of Alberta), Barbara Conner-Spady ‘yes’ or ‘no’. Students also responded to eight statements using a scale from (University of Alberta), Lionel Schachna (Austin Health, Australia), 1 (disagree) to 5 (agree) regarding their confidence in performing the GALS Annelies Boonen (University of Maastricht, The Netherlands) exam relative to other clinical exams, and the usefulness of the training video Background in learning the screening exam. The PASS constitutes an absolute level of patient well-being. We have previ- Results Three statements on the GALS questionnaire (scale 1-5) pertaining to ously shown that PASS thresholds for pain and function were unexpectedly the ease of learning the GALS examination, the effectiveness of the DVD as high in AS suggesting coping as a potential factor in achieving PASS. a learning tool and whether the DVD should continue to be distributed were Objective To examine the independent contribution of perceived locus of answered by 113, 110 and 112 students, respectively. Mean scores of 4.65/5, control as a reflection of coping to attainment of PASS in AS. Methods 4.21/5 and 4.32/5 indicated that the GALS examination was easy to learn, was AS Patients completed a postal questionnaire that included self- reported assessments of pain, fatigue, disease activity (BASDAI), function an effective learning tool and should continue to be distributed, respective- (BASFI), patient global, the Rheumatois Attitudes Index (RAI) ly.The mean score of students’ confidence in their ability to complete the Helplessness Subscale (scoring range 0-25 (more helplessness)), and a GALS screening exam was 4.29/5 in comparison to performing the cardio- question (yes/no) asking about satisfation with their current disease state vascular exam (4.53/5), respiratory exam (4.54/5) and GI exam (PASS). We used both hierarchical and stepwise conditional logistic regres- (4.34/5).Students’ performance on the GALS OSCE station obtained in sion to assess the independent contribution of coping to attainment of PASS. September 2005 and March 2007 revealed mean scores improved from In the first model we included age, sex, and disease duration, in the second 5.25/10 obtained in September of 2005 to 7.53/10 in March 2007. P value is we added the ASAS core measures, and in the third we added the helpless- < 0.001. ness questionnaire. Conclusion Results here show a significant improvement in performance on Results PASS data was available on 466 patients from Canada and Australia the GALS OSCE station suggesting that McMaster students found the GALS of whom 305 (65.5%) reported being in PASS. Helplessness was significant- to be a relatively simple skill to learn in their musculoskeletal unit and were ly higher in PASS- (mean (SD) 16.6 (4.2)) as compared to PASS+ (mean (SD) able to retain this knowledge in their graduating year. The questionnaire indi- 10.6 (4.5)) patients (p<0.0001). Strong correlation was observed between cates that students found the GALS DVD helpful to their learning of the helplessness and BASDAI (r = 0.56), BASFI (r = 0.48), and fatigue (r = 0.50) GALS exam. Regardless of which specialty new medical graduates choose, (all p <0.00001) and moderate correlation with ASQol (r = 0.30), patient glob- they will have the skills to screen for musculoskeletal disorders in a fast and al (r = 0.20), total back pain (r = 0.19), and nocturnal back pain (r = 0.18) (all efficient manner. p< 0.001). In hierarchical regression, adjusting for age, sex, disease duration and the ASAS core measures, helplessness contributed independently to 98 attainment of PASS (OR 0.79 (95% CI: 0.74-0.85); p < 0.0001). Other sig- CNS Wegener’s Granulomatosis Presenting with Bell’s Palsy nificant predictors were BASDAI (OR 0.72 (95% CI: 0.57-0.90); p = 0.005), Mark Matsos (McMaster University), Rajendra Carmona (McMaster and disease duration (OR 1.04 (95% CI: 1.01-1.06); p = 0.009). In stepwise University), Nader Khalidi (McMaster University), Simon Carette regression, helplessness, BASDAI, BASFI, and patient global independently (University of Toronto) contributed to attainment of PASS. In linear regression analysis, helplessness We report a 69-year-old patient presenting with a relapse of Wegener’s contributed 7% and ASAS core measures 30% to the variance in PASS.

Downloaded on September 27, 2021 from www.jrheum.org B Exp B P value 95% CI Methods The ACPAC program is a unique, rigourously evaluated post-grad- Upper Lower uate, interprofessional academic and clinical training program in muscu- BASDAI -.423 .655 <0.0001 .561 .764 loskeletal disease/arthritis management. It is a CME certificate, adult-learn- BASFI .027 1.027 ns .911 1.158 ing based program delivered in episodic (one week/month), format across a Patient Global -.145 .865 0.005 .782 .957 ten month period. Measurement of change in skills and knowledge in the Coping -.232 .793 <0.0001 .741 .848 2005-2007 cohorts involved rigourous baseline and end-program theory and Constant 6.172 479.163 <0.0001 practical skills examination. Surveys were issued to the ACPAC trainee at Conclusion Perceived locus of control (helplessness) is a significant inde- baseline, mid-point and end program, as well as at 6 and 12 months follow- pendent factors in achieving PASS in patients with AS and may represent a ing graduation to capture change in practice patterns across and subsequent to target for intervention. the training program. An externally applied (arm’s length) interview of the ACPAC trained graduate and relevant stakeholders, including physicians and 100 administrators, was undertaken at 12 months following graduation to identify Assessment of Unmet Needs in the Design of Randomized Controlled barriers and enablers to the implementation of these new practice roles in Trials and the Lack of Generalizability for Scleroderma Treatment arthritis care. Sai Yan Yuen (University of Western Ontario, London, ON), Renata Villela Results Extensive evaluation of the 2005-2007 cohorts (n=10 trainees) has (University of Western Ontario, London, ON), Janet Pope (University of been integral to early program outcome, with significant change demonstrat- Western Ontario, London, ON) ed in skills and knowledge measured by practical skills (p<.001) and theory Objective To determine the generalizability of randomized controlled trials exams (p<.001) at program completion. Qualitative analysis of surveys issued (RCTs) in the treatment of systemic sclerosis (SSc) using the Canadian at 6 and 12 months post-graduation identified new, institution-based models Scleroderma Research Group (CSRG) database. of arthritis care which incorporate the ACPAC graduates’ expanded scope of Methods Articles related to SSc (1958 to 2006) were identified using the practice roles. Clear themes in terms of barriers and enhancers in these three PubMed database. Protocols from unpublished RCTs were also included. unique clinical settings are reported. Articles were excluded based on the following criteria: not a RCT, mixed pop- Conclusion The ACPAC program is offered at a critical time in the context of ulation and not in English. Trial quality was scored and key points on trial rapidly changing health care delivery, producing highly skilled advanced design, including inclusion and exclusion criteria, were recorded. The inclu- practice practitioners (APPs), central to development of innovative models of sion/exclusion criteria were compared with the CSRG database to determine chronic disease management (arthritis). Extensive evaluation of the ACPAC the proportion of SSc patients who would theoretically be eligible for these trainees and program is integral to measuring the outcome process. trials. Articles were also classified into subcategories according to the target Triangulation of responses of stakeholders (physicians and administrators) as system. The CSRG database contains 438 SSc patients from 14 Canadian cen- well as the ACPAC trained practitioners at 12 months identified clear barriers ters. Eligibility criteria were excluded from the analysis if they were not and enablers to changes in models of arthritis care. Changes in interprofes- available in the CSRG database or if more than 50% of the data were missing sional dynamics within these new models of arthritis care delivery, and eval- (except for pulmonary arterial hypertension criteria, such as right heart uation of outcome of the episodic delivery of this rigourous post graduate catheterization). Results were in median (%) and mean (%) with 95% confi- clinical and academic training program is of current interest. dence intervals [95% CI]. Results In total, 210 articles were evaluated and 73 were ultimately select- 102 ed for inclusion in this paper. The mean (%) of patients eligible were 35% Predictors of Improvement in Scleroderma: The Relationship of Low Self [95% CI 17,53] for SSc associated with Raynaud‘s phenomenon (n=13 trials), Reported Disability (Measured by the HAQ) and Subsequent 24% [95% CI 1, 47] for digital ulcers (n=6 trials), 48% [95% CI 27, 68] for Improvement of Disease Status in Clinical Practice gastrointestinal (GI) (n=6 trials), 32% [95% CI 20, 43] for overall disease Elizabeth Lawrence (University of Western Ontario, London, ON), Janet modification (n=25 trials), 6% [95% CI 4,8] for pulmonary arterial hyperten- Pope (University of Western Ontario, London, ON), Zeyad Al Zahraly sion (n=13 trials), 2% [95% CI 0, 4] for interstitial lung disease (n=4 trials) (University of Western Ontario, London, ON), Murray Baron (Jewish and 38% [95% CI 12, 64] for other categories (n=6 trials). Results in median General Hospital, Montreal, PQ) (%) and mean (%) were similar. We assessed trial quality with a 5 point scale, Objective To determine if a low baseline Health Assessment Questionnaire which was combined into 3 subsets. Those trials that were generalizable to (HAQ) score (< 1.0), can predict improvement in scleroderma (both limited more patients with SSc had less trial quality, confirming the trade-offs and diffuse, of both early and longer disease duration) in clinical practice over between highly selected inclusion/exclusion criteria and unmet needs (gener- one to two years. alizability) (p=0.0022). Methods Patients were from the scleroderma clinic at St. Joseph’s Health Conclusion Except for GI trials, <38% of SSc patients would be suitable to Centre in London, ON who had completed at least two HAQs and the enter RCTs. SSc lung disease studies had the least percent of patients eligi- Modified Rodnan Skin Score (MRSS), a 100mm VAS scale of overall disease ble. Better trial design yielded less % of SSc patients eligible. We need RCT activity and a 5-point Likert scale (much worse, worse, same, better, much design that includes many patients with SSc as there are few proven treat- better). We calculated the mean and median HAQ for both limited and dif- ments and trials typically do not include the majority of patients nor are they fuse scleroderma at their initial and follow-up visits and the change in HAQ generalizable to most patients suffering from SSc. and compared this to the changes in the other outcome measurements and physician assessment. The main data of interest were the correlation coeffi- 101 cients between baseline HAQ and changes in disease activity at one year. Evaluation and Outcome of the Advanced Clinician Practitioner in Other data from two years were explored between subsets. A p-value of 0.05 Arthritis Care Program was considered significant. Rachel Shupak (St. Michael’s Hospital), Rayfel Schneider (The Hospital for Results One hundred and twenty SSc patients had a baseline HAQ in the clin- Sick Children), Jodi McIlroy (CEHPEA), Katie Lundon (St. Michael’s ic: 38 < 3 years duration at first HAQ; 49 with diffuse SSc; 20 diffuse SSc Hospital) with early disease; 71 with limited SSc; 18 limited SSc with early disease. Objective The objectives are 1. to present outcome data for the 2005-06 and The mean age was 58±1.0 (SEM) and 82% were female. A low HAQ when 2006-07 ACPAC program graduates (n=10) and 2. qualify change in practice first available was predictive of improvement the following year (Year 1) by roles for the 2005-2006 cohort (n=5) identified at 6 and 12 months following physician assessment ( better vs. same or worse) in the overall group and graduation as new models of arthritis care develop in academic, non-aca- when studying only early SSc. In diffuse SSc only early disease was signifi- demic, and remote community healthcare settings across Ontario. cant and in limited SSc early disease was not significant. To determine if the

Downloaded on September 27, 2021 from www.jrheum.org results were generalizable they were validated in the CSRG database (n=438): Results The percentages of patients who scored ≥ 16 and ≥ 23 on the CES-D 294 patients had baseline HAQs, 262 at Year 1 and 112 at Year 2 where 1/3 were 35.1% and 18.1%, respectively. Patients with less education, patients had a disease duration of ≤ 3 years and had diffuse SSc. The results from the who were not married, patients with higher physician-rated overall disease CSRG cohort were similar to the single SSc clinic. severity, and patients with more tender joints, more gastrointestinal (GI) Conclusion The HAQ is a simple questionnaire that can be helpful if the symptoms, and more difficulty breathing had significantly higher total CES- score is low in predicting improvement over the subsequent year in early scle- D scores. As a group, specific symptom indicators (tender joints, GI symp- roderma. It is less predictive in long standing disease. The HAQ should be toms, breathing) predicted the most incremental variance in depressive symp- used in all scleroderma patients as a tool to help determine severity of disease toms (∆R2 = 14.2%, P < 0.001) despite being added to the model after demo- and predict outcomes over the near future. graphic, socioeconomic, and global disease duration/severity indicators. Conclusion High levels of depressive symptoms are common in patients with 103 SSc and are related to overall SSc disease severity, as well as specific medical Prevalence and Risk Factors for Fragility Fractures in Systemic Lupus symptoms. Screening for depression among patients with SSc is recommend- Erythematosus ed, although more research is needed to determine the best method for doing Robert Goldberg (University of Toronto ), Dominique Ibanez (University of this. Successfully treating dypsnea, gastrointestinal symptoms, and joint pain Toronto), Murray Urowitz (University of Toronto), Dafna Gladman may improve mood, although this has not yet been demonstrated. (University of Toronto) Objective To determine the prevalence and evaluate risk factors for the devel- 105 opment of non-vertebral fragility fractures, defined as a fall from standing Risk Factors for the Development of Atherosclerotic Vascular Events in height or less, among patients with systemic lupus erythematosus (SLE). Women with Systemic Lupus Erythematosus Methods SLE patients who suffered a non-vertebral fragility fracture from Robert Goldberg (University of Toronto), Dominique Ibanez (University of January 2002 to August 2007 and who underwent a dual-energy X-ray Toronto), Mandana Nikpour (University of Toronto), Dafna Gladman absorptiometry (DEXA) scan 1-year prior or subsequent to the clinic visit (University of Toronto), Murray Urowitz (University of Toronto) at which the fracture was reported were identified among a large cohort of Objective As the mechanisms of accelerated atherosclerosis in systemic SLE patients. Bone mineral density (BMD) status was defined based on the lupus erythematosus (SLE) remain unclear, we characterized the incidence of WHO classification. Each SLE patient with a fragility fracture was com- atherosclerotic vascular events (AVEs) among SLE patients and non-SLE pared to two sex-, age-, and bone mineral density (BMD)-status matched controls followed over 7-9 years and evaluated risk factors for the develop- SLE patients without fragility fractures. Associated features (disease dura- ment of AVEs. tion, SLEDAI-2K, SLICC/ACR damage index (SDI), and use of steroid, Methods 250 SLE women from a large lupus clinic in Toronto and 250 age- immunosuppressive and other therapy), at the time of DEXA and over the matched non-SLE women controls from a hospital-based family practice unit, 3 years prior to DEXA were compared using paired t test and McNemar both without a prior history of AVEs at study onset, were followed for the tests . development of AVEs, defined as either myocardial infarction, angina, stroke, Results A total of 730 patients attended the University of Toronto Lupus transient ischemic attack or peripheral vascular disease. All participants Clinic from 2002-2007. 26 patients suffered at least one non-vertebral fragili- underwent detailed clinical and biochemical assessments at baseline. The ty fracture. 16 patients had a DEXA scan 1-year prior or subsequent to the development of AVEs was confirmed through telephone interview and chart first reported date of the fracture. Among these patients, 9 had osteopenia and review for control patients and through clinic visits every 2-6 months for SLE 7 had normal BMD. Predictors for the development of a fragility fracture patients. All AVEs were verified with patient medical records. The role of were shorter disease duration (11.1+/-5.8 vs. 14.3+/-7.6, p=0.05) at the time baseline lipid subfractions, other metabolic risk factors, lifestyle variables, of DEXA, and higher adjusted mean SLEDAI-2K (6.13+/-2.89 vs. 4.33+/- and demographic characteristics in relation to the development of AVEs was 2.87, p=0.01) and use of steroids (87.5% vs. 68.8%, p=0.03) or immunosup- assessed using a time to event multivariate analysis. pressive therapy (62.5% vs. 34.4%, p=0.02) three years prior to DEXA. 10 of Results Information was available for 248 of the SLE patients and 238 of the 16 patients with fragility fractures had x-rays of the hip or spine with findings controls. 12 AVEs among non-SLE control participants and 28 AVEs among such as degenerative disease in the lumbar spine, degenerative disease of the SLE patients were identified (Hazard Ratio (HR) 2.36, p=0.001). Significant hip and avascular necrosis of the hip with bony collapse that may have led to predictors for the development of an AVE were older age (HR 1.085, spuriously high BMD levels. p<0.0001), family history of an AVE (HR 2.779, p<0.0027), and SLE itself Conclusion Fragility fractures occurred in 16 SLE patients in the absence of (HR 3.523, p=0.0006). C-reactive protein and homocysteine were not inde- osteoporosis. Risk factors for the development of fragility fractures were pendent predictors of AVEs. shorter disease duration as well as higher disease activity and the use of Conclusion SLE women are at an increased risk for the development of steroid and immunosuppressive therapy in the 3-years prior to the fracture. AVEs. Predictors of AVEs were older age and family history of AVEs. SLE is Degenerative disease in the spine or hip may have contributed to an apparent an independent risk factor for the development of AVEs. normal BMD. Patients with fragility fractures and normal BMD should have BMD measured at sites other than hip or spine. 106 Development of a Web-based Screening Tool for Early Rheumatoid 104 Arthritis — ERASE: the E-Triage RA Study in Early Arthritis Prevalence and Clinical Correlates of Symptoms of Depression in Walter Maksymowych (University of Alberta), Alberta Rheumatologists Patients with Systemic Sclerosis (Alberta) Brett Thombs (McGill University), Marie Hudson (McGill University), Background : The lack of time devoted to MSK training means that primary Suzanne Taillefer (McGill University), Murray Baron (McGill University) care physicians have limited expertise in identifying early RA. Patients with Objective To assess the prevalence and predictors of symptoms of depression MSK disorders increasingly turn to the web in attempts at self-diagnosis but in a large sample of patients with systemic sclerosis (SSc). validated screening tools for serious disorders such as RA are not available. Methods Cross-sectional, multi-center study of 376 SSc patients from the Objective To develop and provide preliminary validation data for a web- Canadian Scleroderma Research Group Registry. Patients were assessed with based screening tool (ERASE) for early RA. the Center for Epidemiological Studies Depression Scale (CES-D) and Methods Items for ERASE were identified following a Delphi consensus of through extensive clinical histories and medical examinations. Hierarchical Alberta rheumatologists who were asked to provide questions exactly as they multiple linear regression was used to assess the relationship between would be elicited during a patient interview. Consensus on the final list of sociodemographic and clinical variables with symptoms of depression. questions was obtained after 3 rounds of electronic voting. ERASE was

Downloaded on September 27, 2021 from www.jrheum.org administered in paper format to consecutive new patients attending an outpa- Criteria set Sensitivity % Specificity % LR(+) [95%CI] LR(-) [95%CI] tient rheumatology clinic before evaluation by the rheumatologist. Calin (4/5) 85 35 1.3[1.1-1.6] 0.4[0.3-0.7] Rheumatologists were asked to rate the probability of RA on a 0-10 scale after Q3 and Q1/Q4 45 91 5.8[2.2-12.2] 0.6[0.5-0.7] completion of their evaluation. Significant items from univariate analyses Q3 and Q1/4 duration were then tested in analyses based on multivariate logistic regression and ≤ 6 years 54 95 11.25[1.6-77.4] 0.5[0.4-0.7] ROC curves to identify a model with the questions considered to be most important in discriminating between those diagnosed with RA and those who 108 were not. A score of 5 on the NRS for RA constituted the dependent vari- Longitudinal Expression of Interferon Responsive Elements in SLE able. This was also used to apply weighting and a scoring tool that could be Patients Does Not Correlate with Disease Activity tested for discrimination in ROC analysis. Carolina Landolt-Marticorena (Toronto Western Research Institute), Gabriel Results The Delphi consensus resulted in 7 items thought to have both posi- Bonventi (Toronto Western Research Institute), Alla Lubovich (Toronto tive and negative predictive value for RA. We tested ERASE in 124 consecu- Western Research Institute), Thulasi Unnithan (Toronto Western Research tive newly referred patients of whom 21 were rated as having RA. Logistic Institute), Dafna Gladman (Toronto Western Research Institute), Murray regression identified the following items as being significantly associated Urowitz (Toronto Western Research Institute), Paul R. Fortin (Toronto with RA: self-reported distribution of joint involvement (OR for MCP = 34, Western Research Institute), Joan E. Wither (Toronto Western Research wrist = 6), duration of symptoms (weeks/months versus years, OR = 5), Institute) presence of any two of jaw pain, irritable bowel syndrome, chronic fatigue, Objective Elevated expression of IFN responsive elements has been noted in daily headaches, (JICH) (OR = 0.01)). ERASE was further developed as a the peripheral blood of SLE patients and appears to correlate with disease screening index based on a weighting of these items ((4 for any MCP activity. In this study we examined the utility of the interferon signature as a involvement)+(2 for any wrist involvement) + (2 for duration suitable biomarker in SLE. weeks/months) +( -3 for any 2/4 of JICH)). ROC analysis based on ERASE Methods Patients (n = 96) satisfying ≥ 4 ACR criteria were recruited from the revealed an AUC of 0.93, sensitivity 95%, specificity of 76%, using a cut- University of Toronto Lupus Clinic and followed longitudinally over a 12 off score of 2.5. month period. Healthy controls (n =11) were also recruited. Peripheral blood Conclusion Our preliminary data shows desirable properties for a simple and clinical information was obtained for all study participants at the time of screening tool for RA (high sensitivity and very good specificity). The web recruitment and at subsequent patient encounters (n = 27). Disease activity format is currently being tested at www.arthritisdoctor.ca. was measured by the SLEDAI-2K. RNA was isolated from peripheral blood and reverse transcribed into cDNA using a ABI high capacity kit. Levels of 5 107 IFN inducible genes (IFIT5, LY6, ISG15, MX1, OAS1) were measured by Development of Diagnostic Criteria for Inflammatory Back Pain in qRT-PCR using Taqman Low Density Arrays and normalized to a housekeep- Ankylosing Spondylitis Based on a Simple 2-Item Questionnaire ing gene (GAPDH). Expression scores from individual IFN inducible genes Stephanie Keeling (University of Alberta), Barbara Conner-Spady were summed to produce a global IFN score. Statistical differences between (University of Alberta), Anthony Russell (University of Alberta), Walter groups where determined by the Mann-Whitney test. Maksymowych (University of Alberta) Results All five IFN -induced genes were expressed at significantly higher Background : Diagnostic criteria for inflammatory back pain (IBP) in AS levels in SLE patients as compared to healthy controls (p < 0.0001) and were have been proposed based on items from the history although this has been elevated even in patients with clinically quiescent disease (SLEDAI = 0, p = determined by patient interview and the questions eliciting this information 0.0005). The global IFN score correlated with high disease activity (SLEDAI have not been standardized and then validated. ≥7) at the initial patient encounter (p = 0.0339). Of the 27 patients with more Objective To develop a candidate set of diagnostic criteria based on stan- than one encounter, 14 had a change in their SLEDAI ≤ 2 (stable) and 13 had dardized questions and to compare them with the Calin criteria for IBP. a change in their SLEDAI ≥ 6 (flare or remission). In the majority of patients Methods A set of 5 questions (Q1-5) was drafted and standardized by con- with stable disease (n = 10) or a clinically meaningful change in their disease sensus exactly as they are posed by local experts in AS to patients during status (n = 10) there was no associated change in their global IFN score. elicitation of the history. These elicit information on diurnal variation in Conclusion Although interferon-inducible genes are highly expressed in SLE degree of stiffness and overall symptoms, nocturnal awakening due to pain, patients fluctuations in disease activity are not mirrored by alterations in the and usual impact of exercise and rest.A questionnaire with this set of 5 ques- global IFN score. Our observations suggest that patients have an “IFN set- tions was administered in random order with the Calin questions to consec- point” which remains static despite changes in clinical disease manifestations. utive patients with established causes of back pain attending the rheumatol- Patients with a high “IFN set-point” may represent a sub-group of patients ogy clinic (AS = 200 (males = 148, mean symptom duration of 15 years), with more severe disease and poorer long-term outcome. mechanical low back pain (mLBP) = 64 (males = 24, mean symptom duration of 14 years). Various combinations of questions were tested by calculat- 109 ing sensitivity, specificity, positive (LR+) and negative likelihood ratios (LR- Molecular and Cellular Changes in RA Synovium Associated with ) and by comparing with the Calin (4/5) criteria. Results were also stratified Infliximab Therapy according to sex and tertiles of symptom duration (≤6, 7-18, ≥ 19 years). Navjot Dhindsa (University of Manitoba), Guoping Ma (University of Patients also completed a 0-10 NRS pain scale to examine the impact of pain Manitoba), Keng Wong (University of Manitoba), Donna Hart (University of level. Manitoba), Warren Froese (University of Manitoba), Hani El-Gabalawy Results Overall, the Calin criteria were of much less diagnostic value than (University of Manitoba) several combinations of standardized questions. A simple 2-item criterion set Purpose The clinical response of RA patients to infliximab therapy is vari- (Q3 and Q1/Q4) that evaluated diurnal variation in overall symptoms (worse able, with some patients achieving remission, while others continue to have in morning versus other times (Q3)) plus either diurnal variation in stiffness residual synovitis. Although the effects of infliximab on the synovium have (worse in morning versus other times) (Q1) or alleviation with exercise (Q4) been explored, patient populations studied have been heterogeneous. We performed best, especially in females where specificity was 100% and in therefore evaluated the synovial effects of infliximab in a cohort of RA those in the lowest tertile of symptom duration. patients who were incomplete responders to methotrexate. Conclusion A simple 2-item criterion set based on standardized questions Methods A total of 10 patients with RA who had an incomplete response to performs better than established criteria for IBP and is of particular value in methotrexate ≥ 15 mg/wk were recruited to the study. Patients underwent a early disease, where the bigger diagnostic problem resides. . Additional ques- baseline (T0) arthroscopic synovial biopsy and then infliximab therapy was tions did not improve diagnostic value. initiated as per currently accepted clinical guidelines (3 mg/kg at week 0, 2,

Downloaded on September 27, 2021 from www.jrheum.org 6, every 8 weeks thereafter). A second arthroscopic biopsy was performed at the WLQ was not different in patients with or without sick leave or with full week 12 (T1), and patients were then followed clinically for a total of one or partime work or with lower or higher educational level. year. H&E stained sections of synovial tissue before and after therapy were Conclusion In Canadian patients with AS, employment rate is not different analyzed for inflammation scores under 6 categories: lining hyperplasia, compared to the general population. However, patients report 1.7 more days angiogenesis, perivascular infiltrates, focal aggregates, diffuse infiltrates, and annual sick leave and experience physical and time demands while being at fibrosis. Immunohistological staining for macrophages (CD68), T cells work. More research into presenteeism and effects on QoL and productivity (CD3), and B cells (CD20) was quantified using ImagePro analysis software. costs is required. A portion of the sample was used for RNA extraction and gene expression profiling (Illumina, 48,687 probe sets, Ellipsis, Toronto). Raw microarray 111 expression data was normalized and statistical analysis was performed using Use of Cyclooxygenase-2 (COX-2) Inhibitors After Acute Myocardial Significance Analysis of Microarray (SAM). Comparisons of T0 and T1 Infarction: What Is the Impact on Death and Cardiovascular Outcome? immunohistological scores and gene expression data was performed using Alain Vanasse (Université de Sherbrooke), Josianne Courteau (Université de paired analyses. Sherbrooke), Danielle Pilon (Université de Sherbrooke), Artur de Brum- Results The characteristics of the cohort were: age (mean) =48.1±14 yrs, all Fernandes (Université de Sherbrooke) patients were females; disease duration (median) = 3.5 (range 1-21). The Objective The objective of the study was to measure the impact of exposition overall change in DAS was T0 = 6.4 ± 1.5 to T1 = 4.9 ± 2.3. In total, 5 to coxibs (Rofecoxib and Celecoxib) on mortality and recurrent acute patients had a EULAR “good” response (mean decrease in DAS = 3.2) and 5 myocardial infarction (AMI) in individuals hospitalized for an AMI between patients had “no response” (mean change in DAS = 0.1). Analysis of the 2000 and 2002 in Quebec. histopathologic parameters showed that perivascular infiltrates had the largest Methods The cohort was constituted of all “ new” patients aged 66 years and overall reduction after infliximab therapy, athough no significant differences older living in Quebec, who survived a hospitalization for an AMI (ICD-9 could be identified between responders and non-responders. A paired analy- code 410) in Quebec between 2000 and 2002. Main variables were all-cause sis of the baseline and 12 week synovial samples using a false discovery rate death, cardiovascular death (ICD-10 I20-I25, I44-I52) and hospital readmis- <10% demonstrated 129 significantly down-regulated genes in the 12 week sion for AMI. Several definitions of drug exposition were considered. samples, including multiple HLA genes, TNF, and the macrophage associat- Covariables included age, sex, year of cohort entry, hospital length of stay, ed marker CD14. A total of 293 genes differentiated responders from non- revascularization at index hospitalization, comorbidity index, exposition to responders in the 12 week biopsies. NSAIDs, and exposition to cardio-protective drugs. Cox proportional hazard Conclusion Differences in the synovial cellular composition and gene expres- models with time-dependent covariates were used. sion profile of may provide the framework for selecting patients for inflix- Results 17,193 patients aged 66 years and older survived a hospitalization for imab therapy. AMI in Quebec between 2000 and 2002. During the 2-year follow-up, 4084 (23.8%) patients died, 2018 (11.7%) from cardiovascular cause, 1836 110 (10.7%) were readmitted for an AMI, 3849 (22.4%) claimed at least one coxib Worker Productivity in Ankylosing Spondylitis: Absenteeism and prescription during the follow-up period. Cox proportional hazard models Presenteeism adjusted for the other covariables show an increased risk of recurrent AMI in Walter Maksymowych (University of Alberta), Barbara Conner Spady Rofecoxib users without increasing the risk of cardiovascular death at 2 years, (University of Alberta), Annelies Boonen (University of Maastricht, The although there is an increased risk of all-cause death. No increased risk for Netherlands) recurrent AMI or death was observed for Celecoxib users. Background : Worker productivity is an important outcome since it con- Conclusion The study shows an increased risk of recurrent AMI in rofecoxib tributes to the well-being of the individual patients and since it is associated users without increasing the risk of cardiovascular death at 2 years, although with costs to society. No information is available on employment rate and there is an increased risk of all-cause death. No increased risk for recurrent sick leave in North American AS patients when compared to the general pop- AMI nor death was observed for celecoxib users. Further studies are needed ulation. Moreover, the difficulties that AS patients encounter when being at to better understand the mechanisms implicated in these effects. paid work (presenteeism) have never been reported. Objective To assess employment rate and sick leave in Canadian patients 112 with AS when compared to the general population and to explore difficulties Subsequent Biologic Therapy Survival and Reason for Discontinuation in patients encounter when being at work. Patients Who Have Discontinued Infliximab Therapy Methods Patients with AS from Alberta completed a postal questionnaire that Cheryl Barnabe (University of Calgary), Susan Barr (University of Calgary), included questions on employment status, days sick leave and the Work Liam Martin (University of Calgary) Limitations Questionniare (WLQ-25). The WLQ contains 25 items that Objective Determine the duration of subsequent biologic treatment and rea- assesses the proportion of time (0 to 100%) patients encounter over the past 2 son for discontinuation in patients previously treated with infliximab. weeks at work due to health problems in each of 5 domains (1) time pressure Methods A prospective longitudinal observational cohort of patients receiv- demands, (2) physical demands, (3) mental demands, (4) interpersonal ing infliximab therapy at teaching hospitals in Calgary, Alberta, has been demands and (5) job output demands. Employment ratios were calculated by maintained since the initiation of infusions in 2000. All courses of biologic indirect standardisation, adjusting for age and gender with the general popu- therapy subsequent to infliximab therapy were analyzed for treatment dura- lation. Days sick leave in the last month were annualised and compared with tion and reason for discontinuation. national sick leave. Results the WLQ was explored for each of the 5 domains. Results A total of 75 patients received infliximab (INF) as their first biologic Results 185 patients returned the questonnaire. 68% were male, mean age and were subsequently exposed to another biologic agent, including etaner- 49.2 (11.2) years was and mean disease duration 14.6 (sd 11.2) years . cept (ETN; n=61), adalimumab (ADA; n=31), rituximab (RIT; n=15), or abat- Employment ratios were 1.03 [95%CI 0.95-1.130] and 1.08 [95%CI 0.89- acept (ABAT; n=2). The average duration of INF use was 1.7 years, with a 1.27] for males and females respectively. In those with paid work, 17% total of 123 person years (PY) of exposure. Average treatment duration with reported sick leave in the passed month and mean annualised sick leave was subsequent biologics was 2.4 years for ETN (sum 128 PY), 1.1 years for ADA 7.3 days compared to the national average 5.56 days. The WLQ showed that (sum 30 PY), 1.2 years for RIT (sum 16 PY), 0.4 years for ABAT (1 PY). because of AS, patients perceived physical and time-pressure demands in Reasons for discontinuation of INF were primary inefficacy (n=14), second- 70% and 35% of the working time. Mental and job-output demands were per- ary inefficacy (n=27), patient/insurance factors (n=5), or adverse events ceived in 28% and 22% of the time. Interpersonal demands were experienced (n=29), including infusion reactions (n=13), skin reactions (n=6), lupus-like in 18% of the time. Females experience more often interpersonal demands but syndrome (n=5), infection (n=3), and other events (n=2). Patients discontin-

Downloaded on September 27, 2021 from www.jrheum.org ued subsequent biologics for the same reason in 18.7% of cases, including 3 prednisolone was the initial corticosteroid in 81%, with oral Prednisone in the for primary inefficacy (with ETN), 6 for secondary inefficacy (4 with ETN, 1 other 19% of patients. Increasing time to initiate corticosteroids was associ- with ADA, 1 with both), 1 for infusion reaction (with RIT), 1 for skin reac- ated with increasing average length of stay in days (aLOS)- within 2 days: tion (with ETN) and 2 for infection (1 with ETN, 1 with ADA). aLOS 14, between 2-3 days: aLOS 17, and more than 3 days: aLOS 38. Conclusion Patients who discontinue infliximab therapy generally have a Increasing total dose of corticosteroids within the first 3 days of admission sustained response to other biologic agents. A minority of patients will dis- was associated with decreasing aLOS- <499 mg: 52 days, 500-999 mg: 19 continue subsequent therapy for the same reason that necessitated a switch in days, 1000-1499 mg: 19 days, 1500-1999 mg: 15 days, >2000 mg: 11 days. A the first place. similar relationship occurred between the starting dose of corticosteroids (mg/day) and aLOS - < 100: aLOS 25, 250: aLOS 22, 500: aLOS 18, and 113 1000: aLOS 11 days. 60% of patients were started on cyclophosphamide with- Comparison of Continuation Rates and Reasons for Discontinuation in in 3 days. Increasing time to initiate cyclophosphamide therapy was associat- the Initial Cohort of Infliximab Patients to a Contemporary Cohort ed with increasing aLOS – within 2 days: aLOS 11, between 2-3 days: aLOS Treated After 2002 18, and more than 3 days: aLOS 31. Infections occurred in 29%, neutropenia Cheryl Barnabe (University of Calgary), Susan Barr (University of Calgary), in 17%, and thrombocytopenia in 14%. 33% required blood transfusion. Liam Martin (University of Calgary) Conclusion In WG admissions for renal failure, pulmonary hemorrhage or Objective To assess whether patients starting infliximab (INF) prior to both, aLOS markedly decreased with initiation of intravenous methylpred- January 1, 2003 had greater disease severity, and higher rates of complica- nisolone within 48 hours of admission, with use of higher daily starting dose tions and non-response compared to more recent users. (1000 mg), with more than 2000 mg in the first 3 days, and with cyclophos- Methods A prospective longitudinal observational cohort of patients receiv- phamide initiation within 48 hours of admission. (Statistical analysis for sta- ing INF therapy at teaching hospitals in Calgary, Alberta, has been maintained tistical significance to be reported.) since the initiation of infusions in June 2000. Descriptive statistics were used to compare demographics, adverse events and reasons for discontinuation of 115 INF between the two cohorts of patients. INF continuation rates in the two Why are People with Rheumatoid Arthritis (RA) Not Using DMARDs?— cohorts were compared using survival analysis (logrank test). Understanding Gaps in Care Results A total of 139 patients initiated INF therapy prior to January 1, 2003 Diane Lacaille (Arthritis Research Centre of Canada), Pam Rogers (Arthritis (Group A) and 77 patients between that date and January 31, 2007 (Group B). Research Centre of Canada) The majority of patients have rheumatoid arthritis (97.1% Group A, 75.3% Objective In previous research, we found that only 43% of the RA pop used Group B) and established disease (duration 14 ± 9 years Group A, 14 ± 10 a DMARD over 5 yrs and rheumatologist care was infrequent (Lacaille 2005); years Group B). The early cohort had used more DMARDs (methotrexate objectives of this study were to 1) confirm these gaps in care by evaluating 99% vs 84%; azathioprine 27% vs 16%; gold 62% vs 43%; penicillamine disease activity in people not using DMARDs, to ensure DMARDs were indi- 40% vs 17%; sulfasalazine 50% vs 36%) except for leflunomide (37% vs cated; 2) understand the underlying reasons for not using DMARDs and not 69%). The average exposure to INF for Group A was 3.0 ± 2.2 years and for seeing a rheumatologist. Group B 1.3 ± 1.1 years. Survival analysis showed a significantly greater INF Methods A survey was sent to a randomly selected subsample of 6500 from continuation rate in Group A (p=0.01). Reasons for discontinuation were the BC population-based RA cohort identified from administrative data. 2007 adverse events in 40% of Group A and 28% of Group B, including death (4% were ineligible (deceased, incorrect address, age <18 or did not report an MD vs 6%), lupus-like syndrome (7% vs 0%), infusion reactions (15% vs 6%), diagnosis of RA), 1822 (41% of eligible) participated. skin reactions (4% vs 9%), neurologic complications (1% vs 0%) and infec- Results Only 49% had ever used a DMARD (now or past use) and 33% were tion (6% vs 6%). Primary inefficacy occurred in 14% vs 28% and secondary currently on a DMARD. Non-DMARD users had active disease: mean (SE) inefficacy in 27% vs 28% of patients. VAS disease activity: 5.5 (0.07), pain: 4.9 (0.07), fatigue: 5.1 (0.07), RADAI Conclusion Continuation rates for the late cohort of INF patients are signifi- joint score 8.4 (0.2); and reduced physical function: HAQ: 1.6 (0.01). Reason cantly lower than the early cohort. More patients in the contemporary cohort for not using DMARDs were: Not suggested by my doctor (45%); Fear of discontinue therapy for primary inefficacy, perhaps reflecting a tendency to side-effects (26%); Prefer to avoid meds (24%); Don’t think I need it (23%); persist less with one anti-TNF inhibitor and switch to other biologic therapies. Bad past experience: S/E (22%) or LOE (11%); Not aware it prevents joint damage (19%); Cost (13%); and Don’t believe it will help (9%). RA was man- 114 aged by a rheumatologist in 39%, with a mean of 2.7 visits/yr; and by their GP Wegener’s Granulomatosis — Analysis of the Hamilton Inpatient in 44%, mean of 8.6 visits/yr. Reasons for not seeing a rheumatologist were: Experience Prefer GP (43%), Satisfied with RA status (36%), Don’t know what more Raj Carmona (McMaster University), Susan John (McMaster University), rheumatologist could do (33%) or is (13%), Not offered by GP (24%), Not sat- Ganesh Subramanian (McMaster University), Nader Khalidi (McMaster isfied with prior encounter (16%) and various access problems (6-13%). University) Conclusion Our study confirms the gaps in care previously identified with Objective To present a retrospective analysis of admissions for Wegener’s administrative data, namely infrequent DMARD use and rheumatologist care, granulomatosis (WG) (2000–2006 inclusive) to the 4 major hospitals in and shows that people not using DMARDs have active RA, warranting Hamilton, Ontario, Canada. DMARDs as per current guidelines. Most reasons cited for not using Methods Using ICD diagnostic codes for WG, a computerized search of hos- DMARDs are potentially modifiable. Although some access problems were pital databases was conducted. Each chart identified was examined, and identified as barriers to seeing rheumatologists, most related to perceived lack admissions for pulmonary hemorrhage, renal failure or both as diagnosed by of need or awareness. These results emphasize that to improve RA care, the admitting physician, were selected for data extraction. Data was extract- addressing access barriers will not suffice. A mentality shift is needed at the ed using a standard questionnaire developed for this review, and the level of people with RA and GPs that mirrors the recent paradigm shift in RA Birmingham Vasculitis Activity Score for WG Form. treatment. Results Of a total 199 admissions, 21% (n=42) were for pulmonary hemorrhage, renal failure or both. Data presented is for this subgroup. The in-hos- 116 pital mortality rate was 14% (n=6). All deaths occurred in those older than 70 Patient-Reported Health Status Outcome Measures in Rheumatoid years, including 4 patients over 80. 49% of patients were admitted for more Arthritis Patients Using Etanercept or Anakinra than 10 days. The average time to initiate corticosteroids was 1.9 days for Claire Bombardier (Institute for Work and Health; University Health known WG patients, and 3.0 days for new diagnoses. Intravenous methyl- Network), Edward Keystone (Mount Sinai Hospital - Advanced

Downloaded on September 27, 2021 from www.jrheum.org Therapeutics; University Health Network), Boulos Haraoui (Institut de had 530 FDRs (208 siblings, 198 parents, 124 children). The probands with Rheumatologie), Carter Thorne (Southlake Regional Health Center), Majed psoriasis alone reported 73 FDRs with psoriasis and 4 with PsA. The preva- Khraishi (Nexus Clinical Research), Jerieta Waltin-James (Ottawa Hospital), lence was thus 13.4% and 0.7%, respectively. The lambda1 was 6.7 and 2.9, Jerry Syrotuik (Amgen Canada Inc.) respectively. Among siblings the prevalence of psoriasis and PsA was 14.1 Objective To capture prospective patient-reported outcome measures over a and 0.8% and the lambdaS was 7.1 and 3.3, respectively. Probands with PsA two-year period in Canadian patients with rheumatoid arthritis (RA), receiv- reported 71 FDRs with psoriasis and 7 with PsA. The prevalence was thus ing etanercept or anakinra as standard therapy. 13.4% and 1.3%, respectively. The lambda1 was 6.7 and 5.3, respectively. Methods The primary endpoint was response to treatment, evaluated using Among siblings, the prevalence of psoriasis and PsA was 18.3% and 2.4% the Health Assessment Questionnaire Disability Index (HAQ-DI). Secondary and lambdaS was 9.1 and 9.6, respectively. Based on findings from a family endpoints included patient and physician global assessments, the Rheumatoid investigation in PsA where the lambda1 for PsA was 30.4 and lambdaS 30.8, Arthritis Disease Activity Index (RADAI), changes in work productivity, and and the lambda1 for psoriasis 7.6 and lambdas 8.8, it was clear that although safety. Patients were assessed at Baseline, and Months 3, 6, 12 and 24 or End probands report the true prevalence of psoriasis in their FDRs, they underes- of Study. Efficacy analyses were based on a modified intent to treat popula- timate the prevalence of PsA among their FDRs. tion (patients with at least one dose of study drug and one post-Baseline Conclusion Recurrence risk for psoriasis and PsA in FDRs of probands with HAQ-DI measurement). Patients were eligible if they were over 18 years of psoriasis and PsA is high. Probands underestimate the prevalence of PsA in age with active RA and not concurrently on biologics. FDRs. Only a full family investigation in psoriasis and PsA will provide a true Results A total of 325 patients (mean age, 53±12.5 years) were enrolled estimate of the recurrence risk ratio of PsA in probands with psoriasis alone between August 2002 and February 2005 from 47 Canadian centres. Of these and with PsA. 325 patients, 252 initially received etanercept and 73 initially received anakinra, although 1 etanercept patient later switched to anakinra and 15 119 anakinra patients switched to etanercept. Results for the etanercept group fol- Clinical Presentation, Diagnosis, Histologic Features and Treatment for low. Of the 267 patients receiving etanercept, 167 (62.5%) completed 2 years Idiopathic Granulomatous Mastitis (IGM) of treatment. The most common reasons for discontinuing treatment were Isaac Bogoch (University of Toronto), Sharron Sandhu (Sunnybrook Health non-response (42 patients (15.7%)) and adverse events (27 patients (10.1%)). Sciences Centre), Mary Bell (Sunnybrook Health Sciences Centre) HAQ-DI scores improved from Baseline to Months 3, 6, 12 and 24, with a Objective To review the clinical presentation, diagnosis, histologic features mean change of -0.57 (95% CI -0.66, -0.48.) from Baseline to Month 24. and treatment for idiopathic granulomatous mastitis (IGM). HAQ-DI improvement at Month 24 was confirmed with last observation car- Methods A 33 year old south Asian female presented with a left breast mass ried forward. Improvements in productivity were also observed over time, measuring 2 x 2 cm of four months duration. She had no lymphadenopathy or with an 80% decrease from Baseline to Month 24 in the mean number of constitutional symptoms. Ultrasonography and guided biopsy revealed: a missed work days and the number of days prevented from doing normal activ- hypoechoic solid and cystic nodule; multiple simple and complex cysts; and ities. Patient and physician global assessments of disease activity also dilated ducts with internal debris. Serosanguinous fluid drained from the improved, and RADAI scores declined by 3.18 (95% CI 2.86, 3.50) over the biopsy tract following her ultrasound. Magnetic resonance imaging (MRI) same period. The most common adverse events were injection site reaction, revealed an irregular 2 cm mass with rim enhancing cysts and no lym- headaches and upper respiratory tract infections. In the etanercept group, there phadenopathy. Biopsy results demonstrated acute and chronic inflammatory were 16 serious drug-related adverse events in 13 patients and three deaths. cells with multinuclear giant cells and no evidence of malignancy. The histol- Conclusion Baseline demographics were consistent and representative of the ogy was consistent with granulomatous mastitis (GM). Sarcoid, tuberculosis, general rheumatology clinical practice. In this study of RA, patients receiving and fungal infection were ruled out and the patient was treated successfully etanercept experienced improvements in functionality and productivity over a with prednisone 30 mg daily tapering to 0 mg over a 6 month period with two-year period. complete resolution of signs and symptoms. A follow-up MRI four months This study was funded by Amgen Canada Inc. and Wyeth Pharmaceuticals. after her initial MRI, and seven weeks after initiating prednisone therapy revealed a markedly decreased enhancement of the left breast with no mass 117 and residual rim-enhancing cysts. Probands Underestimate the Prevalence of Psoriatic Arthritis in Their Results IGM is a rare, benign breast disease that has a similar clinical pres- Relatives entation to carcinoma of the breast. The hallmark feature of IGM is a histo- Vinod Chandran (Toronto Western Hospital), Joanna Ueng (Toronto Western logic specimen which reveals non-caseating granuloma formation in women Hospital), Sutharshini Shanmugarajah (Toronto Western Hospital), Fawnda presenting with either a breast mass or abscess. IGM presents with a painful Pellett (Toronto Western Hospital), Catherine Schentag (Toronto Western or non-painful breast mass or abscess. Peu d’orange, nipple retraction and pal- Hospital), Cheryl Rosen (Toronto Western Hospital), Dafna Gladman pable axillary lymph nodes have also been described. IGM is diagnosed by (Toronto Western Hospital) breast biopsy and culture. Tuberculosis, fungal infection, sarcoid, foreign body, Objective To determine the prevalence of psoriasis and PsA among first and fat necrosis must be ruled out. A chest X-ray, acid fast stains, and appropri- degree relatives (FDRs) of patients with psoriasis alone and patients with PsA. ate cultures should be performed. Histologic features of IGM are non-caseating Methods 100 consecutive consenting patients with psoriasis alone and 100 granulation tissue with epitheliod histiocytes, microabscesses, Langan’s giant consecutive consenting patients with PsA completed a family history ques- cells and often foreign body giant cells. The optimal treatment approach for IGM tionnaire. Prevalence of psoriasis and PsA in FDRs of probands, according to is unclear. Multiple modalities have been used including high/low dose steroids, probands report, was determined and recurrence risk ratio (prevalence in rel- methotrexate, conservative management, and lumpectomy. atives over the prevalence in general population) was calculated for FDRs Conclusion IGM is a rare benign breast disease of unknown etiology. We rec- (lambda1) and for siblings (lambdaS), assuming population prevalence of ommend that patients be given the option of immunosuppressive therapy or a psoriasis to be 2% and of PsA 0.25%. conservative approach. Immunosuppressive therapy may hasten recovery but Results 185 consecutive patients with psoriasis alone were approached to has well known adverse effects. recruit 100 probands (59 males, mean age 47 years, psoriasis duration 16 years and age at onset of psoriasis 30 years). 180 consecutive PsA patients 120 were approached to recruit 100 probands (50 males, mean age 51 years, pso- Burden of Autoantibodies and Association with Disease Activity and riasis duration 23 years, age at onset of psoriasis 28 years, PsA duration 18 Outcome in Systemic Lupus Erythematosus years and age at onset of PsA 33 years). The 100 Psoriasis probands had 547 Zahi Touma (Toronto Western Hospital), Desiree Tulloch-Reid (Toronto FDRs (241 siblings, 194 parents, 112 children), while the 100 PsA probands Western Hospital), Sergio Toloza (Toronto Western Hospital), Dominique

Downloaded on September 27, 2021 from www.jrheum.org Ibanez (Toronto Western Hospital), Dafna Gladman (Toronto Western Consenting outpatients aged 50 years and older with suspected non-hip Hospital), Murray Urowitz (Toronto Western Hospital), Paul Fortin (Toronto fragility fracture are randomized to either Minimal or Intensive Intervention. Western Hospital) In addition to multiple actions to increase initiation and persistence on treat- Objective To determine whether immunological burden at inception, as indi- ment, Intensive Intervention involves performance of screening tests to iden- cated by multiple autoantibody profiling, correlates with disease activity and tify underlying primary conditions: CBC, serum creatinine, calcium, phos- damage in SLE. phate and alkaline phosphatase, and plasma protein electrophoresis. Results Methods Patients with SLE followed from inception at a single centre of lab screening were reviewed to assess the prevalence of primary conditions between 1992 and 2007 were included. Patients are followed prospectively at in our patients. 2-6 month intervals according to a standard protocol including complete his- Results Over the first 9 months, 355 patients were identified, 30% with hip tory, physical examination and laboratory evaluation, with all items necessary fracture. We report on the lab results from 187 patients: 83 from Intensive to complete the SLE activity index 2000 (SLEDAI-2K) and Systemic Lupus Intervention (peripheral fractures) and 104 with hip fracture. Among the 83 International Collaborative Clinics Damage Index (SDI). Twelve laboratory Intensive Intervention patients, we identified 2 Multiple Myeloma, 2 variables reflecting autoimmune immunological burden included were: posi- Monoclonal Gammapathy of Unknown Significance (MGUS), 2 Severe tive ANA, anti-ds DNA, anti-Smith, anti-RO, anti-La, anti-RNP, ANCA, anti- Kidney Insufficiency (SKI; clearance < 30 ml/min), and 1 Isolated elevation Scl- 70, anti-Jo, antiphospholipid antibodies, Coomb’s test and LE cells. of alkaline phosphatase. In the 104 patients with hip fracture, we identified 2 Patients having 10 or more of these autoantibodies (autoantibody burden) dur- MGUS, 12 SKI, and 1 Primary Hyperparathyroidism. ing the first year were studied; the number of positive antibodies accrued dur- Conclusion Involving orthopaedists as key leaders of a multidisciplinary ing this first year was determined in each patient. Correlations between team implementing a systematic approach to identify patients with OP should autoantibody burden at inception and adjusted mean SLEDAI (AMS) and SDI help to close the current care gap. Primary conditions that have to be consid- at 1 and 3 years after inception were determined using the Pearson correlation ered before initiating treatment are present in 8% (peripheral) to 15% (hip) of co-efficient for linear relationships and chi-square for categories ≤4 and >4 fragility fracture patients evaluated by orthopaedists. This should be taken autoantibodies. into account in any strategy aimed at improving the treatment of patients with Results From 1992-2007, 235 inception patients were identified; of these, fragility fracture. 223 patients had 10 or more autoantibodies assayed within the first year. By Supported by unrestricted grants from Merck Frost Canada and L’Alliance year 1, 223 patients had a mean number of positive autoantibodies of 4.02 ± pour la sante des os (Aventis Canada and Procter & Gamble Pharma) 2.45, and an AMS of 6.61 ± 4.56. At 3 years the numbers were 4.75 ± 2.62 and 5.60 ± 3.37. There was no strong correlation between number of anti- 122 bodies at inception and disease activity by AMS at either 1 year (r = 0.19, p GALS Exam Identifies Musculoskeletal Abnormalities Not Previously = 0.005) or 3 year (r=0.20, p = 0.01, n = 163). No significant correlation could Identified in Routine Family Practice be established between autoantibody burden and disease activity when Karen Beattie (Post Doctoral Fellow McMaster University), Raja Bobba dsDNA was excluded from the analysis (year 1: r = 0.10, p = 0.16, year 3: r (McMaster University), Imaan Bayoumi (McMaster University), David = 0.10, p = 0.23). Correlation analysis between number of autoantibodies with Chan (McMaster University), Inge Schabort (McMaster University), Pauline disease damage (SDI) did not reach statistical significance. There was no dif- Boulos (McMaster University), Walter Kean (McMaster University), Joyce ference in outcomes (SDI and AMS) at 3 years when autoantibody presence Obeid (McMaster University), Ruth McCallum (McMaster University), was considered dichotomously as ≤4 and > 4. George Ioannidis (McMaster University), Alex Papaioannou (McMaster Conclusion Immunological burden in SLE, as reflected by the antibodies University), Alfred Cividino (McMaster University) assessed, was not predictive of subsequent disease activity or damage. Objective To determine if the GALS (Gait, Arms, Legs, Spine) screening tool Further study is needed to establish the possible role of particular autoanti- could identify new musculoskeletal (MSK) pathologies/abnormalities that body clusters in disease manifestations and/or outcomes. had not been previously reported in family practice. Method Patients 65 years of age and older were recruited from an academic 121 family health centre. Rheumatologists performed the GALS exam on all par- Primary Conditions Potentially Affecting Treatment of Osteoporosis in ticipants and recorded the appearance of gait and the appearance and move- Fracture Patients ment of the arms, legs and spine by deeming them normal or abnormal. Gilles Boire (Centre hospitalier universitaire de Sherbrooke), Francois Following the exams, patients’ electronic charts (e-charts), including family Cabana (Centre hospitalier universitaire de Sherbrooke), Michele Beaulieu physicians and radiographic reports and referrals to physical therapy and ter- (Merck Frosst Canada), Dominique Lambert (Procter & Gamble and Aventis tiary care, were retrospectively reviewed in duplicate. Physical abnormalities Canada), Julie Robindaine (Centre hospitalier universitaire de Sherbrooke), identified by rheumatologists were sought in the chart history over the past 2 Noemie Poirier (Centre hospitalier universitaire de Sherbrooke), Line years. Abnormalities not previously documented in the chart were considered Larrivee (Centre hospitalier universitaire de Sherbrooke) “new”. Pain was not considered an abnormality. Two rheumatologists Objective To describe the prevalence of primary conditions potentially affect- reviewed the abnormalities and determined whether they can/should be inves- ing options of osteoporosis treatment in patients with fragility fracture seen tigated further or treated. by orthopaedists Results E-charts were available for 92/99 individuals; 57 women, 35 men, Methods Only 20-30% of women presenting with fragility fractures are sub- mean age 75 (SD=6.1) years. ICD-9 codes revealed 88/92 individuals had sequently investigated and treated for Osteoporosis (OP). The most prevalent previously been diagnosed with an MSK disorder. Ten (10%) participants primary conditions underlying fragility fractures, e.g. deficiencies in sexual were identified with a new gait abnormality, nine requiring further investiga- hormones and vitamin D, do not alter usual treatment strategies that consist tion/referral. One-third of participants (N=30) were identified with at least 1 of calcium and vitamin D supplementation plus antiresorptive agents (most new arm abnormality, the majority (N=84%) being in the fingers/hand. Of 31 frequently bisphosphonates). Primary conditions potentially affecting these arm abnormalities, 7 would require further investigation/referral and 23 simple treatment options may contribute to the reluctance of orthopaedists to would be treated if symptomatic. In the legs, 35 (38%) participants had 46 take OP in charge. OPTIMUS is a 3 year health management program, lead new abnormalities, 18 requiring further investigation and 24 requiring treat- by an orthopaedist and a rheumatologist, whose objective is to improve the ment if symptomatic. Of these, 52% (N=24) were in the toes/foot, 7% (N=3) rate of initiation of and persistence on treatment of OP in patients sustaining in the ankle, 24% (N=11) in the knee, 15% (N=7) in the hip and 2% (N=1) a fragility fracture visiting an orthopaedist at the Centre hospitalier universi- “other”. The prevalence of new spinal abnormalities was 29% (N=27), with taire de Sherbrooke. Consenting inpatients with hip fracture are evaluated by a total of 40 identified, 14 of which would require further investigation/refer- a rheumatologist, who prescribes appropriate investigation and treatment. ral. Scoliosis accounted for 15% of abnormalities (N=6), kyphosis for 30%

Downloaded on September 27, 2021 from www.jrheum.org (N=12), loss of lordosis for 20% (N=8), decreased cervical ROM for 23% Results Eighty-eight women were evaluated. Mean age was 40.0 (standard (N=9), DDD for 10% (N=4) and “other” for 3% (N=1). deviation, SD 14.9) years and mean disease duration was 4.2 (SD 2.1) years Conclusion Results here revealed that the GALS screening tool identified at the end of follow-up. Of these women, 41 (46.6%) were single, 30 (34.1%) new pathologies/abnormalities in patients with previously reported mus- were married or living with a partner, and 17 (19.3%) were divorced, separat- culoskeletal disorders in routine family practice. The arms and legs, ed or widowed. Menarche was reported to have occurred at a mean age of specifically the hands and feet, were those most commonly identified with 12.4 (SD 1.7) years (median 13.0). A total of 120 pregnancies were reported new abnormalities. Of these abnormalities, the majority would require in 53 women, resulting in 15 spontaneous abortions and 77 births. Mean age further investigation/referral or treatment in cases where patients were at first birth was 23.6 (SD 5.6) years. Sixty-eight (77.2%) of the subjects were symptomatic. premenopausal, as of the end of follow-up, and 20 (22.7%) were postmenopausal. In premenopausal women, 11 (16.2%; 95% CI 8.7, 27.5) were 123 current OCP users, and 35 (51.5%) were past users. In comparison, current Early Inflammatory Arthritis Screening Tool Development use in the general population, based on Statistics Canada’s 1996/97 National Mary Bell (Sunnybrook Health Sciences Centre, Toronto), Francis Guillemin Population Health Survey, was 17.8% in women aged 15-49 (95% CI 16.9, (CHU de Nancy - Hôpital Marin, France), Vivian Bykerk (Mt. Sinai Hospital, 18.7%). In most (90%) of postmenopausal women, menopause preceded SLE Toronto), Alex Kiss (Sunnybrook Health Sciences Centre, Toronto), Peter diagnosis, on average by 14.6 (SD 10.5) years. The mean age at menopause Tugwell (University of Ottawa, Ottawa), George Wells (University of Ottawa, in our sample was 43.5 (SD 8.8) years (median 45.0), independent of prior Ottawa) cyclophosphamide use. In comparison, in Canadian women, the mean age at Objective To develop a brief and easy-to-use screening tool for early inflam- menopause has been reported as 51 years (The Canadian Consensus matory arthritis [EIA] and determine face validity and test-retest reliability. Conference on Menopause and Osteoporosis 2002 update, J SOGC 2002; Methods A literature search was performed using National Library of 24:S1-91). Medicine with the following terms: rheumatoid arthritis, inflammatory arthri- Conclusion We present preliminary data on reproductive events in an incep- tis, early diagnosis, mass screening and questionnaires. Leaders in the field of tion cohort of female SLE patients. These data suggest that the prevalence of early inflammatory arthritis were identified from the published literature, OCP use in SLE patients is similar to the general population. Moreover, the review of abstracts from ACR, CRA, and EULAR annual meetings, and by data corroborate previous studies, suggesting that menopause in SLE occurs nomination from professional colleagues. A 3-round Delphi Consensus earlier than in the general population. We are currently expanding our work to Exercise was used to develop and refine the final tool. Face validity and test- further assess reproductive issues in SLE. retest reliability of the tool were determined. Results 584 abstracts were reviewed by 2 reviewers and 47 abstracts were 125 chosen for full article review based on pre-determined criteria. The original 9 Early Inflammatory Arthritis Screening Tool Development and candidate variables were identified from the literature review and expanded Preliminary Validation in Canada to 30 and reduced to 12 through a 3-round Delphi Consensus Exercise. The Mary Bell (Sunnybrook Health Sciences Centre, Toronto), Francis Guillemin 12 variables were then formulated into simple questions appropriate self- (CHU de Nancy - Hôpital Marin, France), Vivian Bykerk (Mt. Sinai Hospital, administration by patients with at least a grade 8 education. Face validity of Toronto), Alex Kiss (Sunnybrook Health Sciences Centre, Toronto), Peter the final variable selection is good as these items bare strong similarity to Tugwell (University of Ottawa, Ottawa), George Wells (University of Ottawa, those previously suggested by experts in the field of early inflammatory Ottawa) arthritis. Twenty-ninepeople with treated EIA, Osteoarthritis or no muscu- Objective To conduct preliminary field validation in Canada of a brief and loskeletal [MSK] complaints were screened on 2 occasions, 1-2 weeks apart, easy-to-use 12 question screening tool for early inflammatory arthritis [EIA] using the newly developed EIA screening tool. Individuals with EIA had a and to determine the sensitivity, specificity, positive and negative predictive high score, people with OA had a medium score, and those with no MSK value of the screening tool. complaints had a low score on the EIA screening tool. The test-retest relia- Methods Patients who had been referred to the general rheumatology clinic bility was good to excellent with an intraclass correlation for the overall at Sunnybrook Health Sciences Centre, to the early arthritis clinic at Mt. Sinai score of 0.97. Hospital for new MSK complaints, and who were on a non-inflammatory Conclusion An extensive literature search and critical appraisal combined waiting list in Thunder Bay were screened via telephone and in waiting rooms with a 3-round Delphi exercise resulted in a 12-question easy-to-use self- using the same12 question screening tool. The primary care diagnosis was administered screening tool with sound measurement properties. The tool is obtained from the referral sheet and the rheumatologist indicated the final currently undergoing field testing in the North American primary care envi- diagnosis on the screening tool. ronment. Results A cohort of 277 subjects was screened in 3 sites, and 150 were evaluated in the rheumatology clinic. Thirty-five patients were diagnosed with 124 inflammatory arthritis on their first visit. In these settings, the EIA screening Reproductive Health Issues in SLE: Preliminary Data tool had a sensitivity [0.74], specificity [0.68], and positive [0.41] and nega- Evelyne Vinet (McGill University Health Center), Christian A. Pineau tive [0.90] predictive values. (McGill University Health Center), Ann E. Clarke (McGill University Health Conclusion A simple, easy to use screening tool with high sensitivity and Center), Sasha Bernatsky (McGill University Health Center) specificity will help in the early identification of patients with inflammatory Background : Because systemic lupus erythematosus (SLE) mostly affects arthritis and improve the triage of patients on the rheumatology waiting list. women of childbearing age, reproductive issues are extremely important. Wider field validation of the tool in the Canadian environment is ongoing. However, up-to-date figures regarding reproductive health in these patients are lacking, particularly in Canada. 127 Objective To characterize reproductive history in an inception cohort of CANaDian Evaluation of Low DosE Infliximab in Ankylosing female SLE patients, and to compare key features (age at menopause and oral Spondylitis (CANDLE)-12 week Magnetic Resonance Imaging contraceptive pill (OCP) use) to general population figures. Evaluation of Spinal Inflammation with the SPARCC MRI Method Methods Consecutive cases of new-onset SLE, presenting to the Montreal Walter Maksymowych (University of Alberta), David Salonen (University of General Hospital lupus clinic from 22/03/2000 to 11/21/2007, were enrolled Toronto), Robert Inman (University of Toronto), Paul Filipow (University of and followed prospectively with annual assessments. At their last visit, Alberta), Robert Lambert (University of Alberta) women were questioned regarding marital status, history of menarche, Objective To evaluate the effect of low dose infliximab on spinal inflamma- menopause, pregnancy, and OCP use. tion scored by MRI in patients with AS. Spinal inflammation is a prominent

Downloaded on September 27, 2021 from www.jrheum.org feature of AS and responds clinically and radiologically to infliximab admin- =0.793) and movement of arms (Pobs =0.760, Ppos =0634, Pneg =0.821). The istered at 5mg/kg. Preliminary data shows that the dose recommended for poorest agreement occurred in the assessment of the appearance of the legs rheumatoid arthritis (3mg/kg) is also clinically effective for AS though effects (Pobs =0.578, Ppos =0.574, Pneg =0.583) and spine (Pobs =0.597, Ppos on spinal inflammation visible on MRI have yet to be described in a placebo- =0.400, Pneg =0.697). Physicians were more likely to agree when the trait controlled trial. was normal than when it was abnormal. Methods This was a 52-week Phase IIIb study conducted in Canada with a Conclusion These results demonstrate satisfactory agreement between physi- 12-week double-blind period during which patients were randomized 1:1 to cians in GALS scoring suggesting that family physicians can efficiently use receive either infliximab 3mg/kg at 0, 2, and 6 weeks or placebo. Patients with the examination in the assessment of populations with a high proportion of active AS who had an inadequate response to at least one NSAID or DMARD musculoskeletal issues. A collaborative meeting between rheumatologists and were eligible to enroll. Spinal inflammation was measured by the family physicians may have improved the agreement. A future large scale Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Index at study will also investigate agreement between family physicians and between baseline and 12 weeks by 2 readers blinded to time point and treatment rheumatologists. allocation. Results A total of 32 patients (16 PBO, 16 IFX) were enrolled. Patients in 129 IFX and PBO arms had similar baseline characteristics. No spinal inflamma- Pilot Study: Evaluation of an Optical Diagnostic Technique, Laser tion was evident at baseline in 3 patients as confirmed by both readers. In Speckle Imaging, to Assess Disease Activity in Affected Hand Joints in PBO patients, spinal SPARCC between baseline and week 12 was relatively Patients with Rheumatoid Arthritis similar with mean value of 18.03 and 18.03, respectively (+14% change). Nicole LaBrie (Queen’s University), Forrester Kevin (University of Calgary), Whereas in the IFX group, spinal SPARCC between baseline and week 12 Martin Liam (University of Calgary) was significantly reduced with mean value of 17.63 and 6.22, respectively (— Objective To determine the ability of LSI to detect changes in joint perfusion 55.8% change) with a p value of 0.0004 between IFX vs PBO groups. A large of actively inflamed joints after therapeutic intervention that are consistent treatment effect was evident, Guyatt’s effect size being 2.11. Improvement with clinical observation. was evident in all patients receiving infliximab that had spinal inflammation Methods Four participants with clinically active inflammation in the small at baseline. Significant associations were noted between change in SPARCC joints of their hands were recruited for the study. Each participant completed score and change in ESR (Spearman’s r = 0.57, p = 0.001) and CRP (r = 0.45, a pre-laser imaging questionnaire to identify confounding variables that could p = 0.012). Reproducibility of SPARCC scores for spinal inflammation was influence blood flow through their peripheral vasculature. A joint exam was high (intra-class correlation coefficient (ICC) for pre-treatment status = 0.89, performed and the actively inflamed PIP and MCP joints of the participants’ for post-treatment status = 0.95, for change score = 0.81). right hands were scanned with LSI (Photokron Inc.). Participants were then Conclusion Treatment with low dose infliximab leads to a large treatment given a corticosteroid injection according to clinic protocol. They returned 7 effect on spinal inflammation scored by the SPARCC MRI method. days later for a repeat joint exam and laser scan. Data was analyzed using Laser Imager Analysis (Photokron Inc.) software. A mean blood flow value was cal- 128 culated for a 1 cm2 area over the dorsal aspect of the involved joints. Pre and Validation of the GALS Musculoskeletal Screening Exam for Use in post corticosteroid perfusion maps were compared for each participant. Primary Care: A Pilot Study Results Of the 4 participants evaluated, 2 showed clinical improvement in all Karen Beattie (Post Doctoral Fellow McMaster University), Raja Bobba the active hand joints, 1 had resolution of inflammation in PIPs but not MCPs (McMaster University), Imaan Bayoumi (McMaster University), David and the final participant showed no clinical improvement in any joints. All the Chan (McMaster University), Inge Schabort (McMaster University), Pauline individual joints across the population that showed clinical improvement had Boulos (McMaster University), Walter Kean (McMaster University), Joyce increased mean regional blood flow. In contrast, the joints that did not Obeid (McMaster University), Ruth McCallum (McMaster University), improve clinically showed a small decrease in mean regional blood flow. The George Ioannidis (McMaster University), Alex Papaioannou (McMaster one participant who had resolution of signs in PIP’s but not MCPs showed University), Alfred Cividino (McMaster University) increased mean blood flow in PIPs and decreased mean blood flow in MCPs. Objective To evaluate the validity of the GALS (Gait, Arms, Legs, Spine) Conclusion We had anticipated that the participants who had shown clinical locomotor screen, a simple, efficient and sensitive MSK exam, in primary improvement in their joint scores would have a measurable decrease in the care by comparing results of patients’ assessments performed by family blood flow to these joints. One of the clinically accepted markers of active physicians with those of rheumatologists. arthritis is increased temperature over the joint, which is thought to be due to Methods Patients were recruited from an academic family health centre by increased blood flow. These results suggest that perhaps our assessment of the searching the clinic’s electronic database for males and females ≥ 65 years. cause of increased joint temperature may not be as simple as previously Participants agreed to be examined by one rheumatologist and one family thought. Further studies with larger populations are needed to determine if in physician. Family physicians (N=3) had no previous exposure to the GALS fact these results are valid. exam and were taught how to perform the exam using an instructional DVD. Rheumatologists (N=4) also received the DVD although they were familiar 130 with the exam. Physicians were asked to evaluate and record the appearance Central Referral and Triage for Rheumatology (CReATe Rheum) in of the participants’ gait and both the appearance and movement of their arms, Calgary: Year 1 Update legs and spine by deeming them normal or abnormal. Scores from the GALS Susan Barr (University of Calgary), Terri Lupton (University of Calgary), screening examination were compared between rheumatologists and family Liam Martin (University of Calgary), for the Division of Rheumatology physicians with the primary outcome being the proportion of observed, posi- (University of Calgary) tive and negative agreement. Kappa statistics were also calculated. Objective To compare referral volumes and wait times before and after Results A total of 99 patients consented to participate; 61 women, 38 men, implementation of Central Referral and Triage for Rheumatology (CReATe mean age 75 (SD=6.1) years. ICD codes revealed 92 of 99 participants had Rheum) in Calgary. been previously diagnosed with an MSK condition. Overall agreement (Pobs Methods All new referrals are received by a single fax, additional data is ) between family physicians and rheumatologists for all aspects of the exam obtained as needed, the referral is triaged by a Nurse Clinician and assigned was 0.698, Ppos =0.614 and Pneg = 0.752. The coefficient of agreement a tentative appointment date with the specified physician or next available (Kappa) was 0.3675 for the composite GALS score. Specifically, higher pro- rheumatologist based on urgency (“estimated wait time”). The physician later portions of agreement occurred in assessment of gait (Pobs =0.784, Ppos reports the date the patient was actually seen since appointments are often =0.813, Pneg =0.676) and the appearance (Pobs =0.742, Ppos =0.617, Pneg moved up (“actual wait time”). Patients requiring expedited care are directed

Downloaded on September 27, 2021 from www.jrheum.org to specialized clinics (i.e. Urgent Assessment, Early Arthritis and Young (IPP). IPP has been shown to directly activate γ/∂ T-cells. Interestingly Adult). Some of the less complex cases are assessed at a Nurse Practitioner statins, which inhibit an enzyme further upstream of IPP in the mevalonate Clinic. A database is used to track all referrals. Wait times for 4083 referrals pathway, have been shown to negate the pro-inflammatory effects of amino- received during the first 12 months of operation (Apr 2006 - Mar 2007) were bisphosphonates. compared to baseline data from a 2005 practice audit of 485 referrals. Wait Conclusion Given the pro-inflammatory nature of aminobisphosphonates times were expressed as the mean (SD) in days and compared using Student’s coupled with the insight that AF appears to be an inflammatory condition, it t tests. is reasonable to postulate that aminobisphosphonates may increase the risk of Results Referral volume has remained constant at ~100 per week since 2005. AF through an inflammatory mechanism. The inflammatory mechanism may An increasing proportion of referrals now request the next available rheuma- be mediated through an intermediate in the mevalonate pathway (IPP), and if tologist (55%) rather than a specific physician. Based on information so, could potentially be prevented with statin therapy. received on the referral, most are classified as routine (25%) or moderate-routine (54%), with the remainder being triaged as moderate (16%) or urgent 132 (5%). In 57% of cases, the referring physician suspected or wished to rule out Systematic Literature Review on the Safety Monitoring and the an inflammatory rheumatic disorder. The central triage process has eliminat- Contraindications of Methotrexate in Rheumatoid Arthritis ed wait list shopping via duplicate referrals to more than one rheumatologist. Judith Trudeau (APHP-Pitie Salpetriere), Claire Bombardier (University of The no-show rate for new patients has decreased from 8% to 6%. In 2005, Toronto) mean (SD) wait times in days were: routine 155 (88), moderate 110 (57), and Objective To perform a systematic review of the literature to answer 2 ques- urgent 29 (46). Since the implementation of central triage, a significant tions: 1- In the general adult RA patients taking Methotrexate, which safety reduction in estimated wait times has been observed compared to 2005 for: monitoring procedures (clinical, laboratory, imaging), assessed at which inter- routine 143 (59) and moderate 77 (53) referrals (p < .001), as well as urgent val of time, can identify all or almost all clinically meaningful serious adverse referrals seen during the second 6 months of operation [18 (17) days; p=.04]. events due to Methotrexate, while being practical, safe and cost-effective? 2- Actual wait times were significantly shorter than estimated wait times for In adults taking weekly Methotrexate for rheumatoid arthritis, what pre- routine referrals [117 (52); p<.00005]. administration work-up (comorbidities, social behavior, physical, laboratory Conclusion Preappointment management of referrals can improve referral and radiographic data, etc.) is necessary for deciding on prescribing quality and triage, identify inappropriate referrals and reduce duplication of Methotrexate or not (e.g. contraindicate Methotrexate administration or not)? investigations. In our centre, central referral and triage has improved ease and These 2 questions were selected by experts from 17 countries participating in timeliness of access, eliminated duplicate referrals and improved efficiency. the 3 E Initiative on the Use of Methotrexate in Rheumatic Diseases. Since implementing this program, we have also observed a significant reduc- Methods Systematic literature review using Medline, Embase, Current tion in wait times for all triage categories. Contents, Cochrane Reviews, manual search of included articles’ bibliogra- phy and of review articles. 131 Results Safety monitoring: We retrieved 857 citations and another 23 from Patients with Rheumatic Diseases Suffer from an Increased Burden of hand searching of their references; 24 met our inclusion and exclusion crite- Both Osteoporosis and Cardiovascular Disease ria and were included for data extraction. None of the included studies were Jason Roberts (University of Toronto, Toronto), Eugene Crystal (University randomized trials of monitoring strategies; all were cohorts or case-control of Toronto, Toronto), Mary Bell (Sunnybrook Health Sciences Centre, studies. The higher quality studies indicate that AST/ALT sensitivity to detect Toronto) liver histologic abnormalities is low; AST/ALT abnormalities have high Objective To propose a link for the increased risk of atrial fibrillation (AF) specificity to detect any histologic abnormality, but almost all abnormalities following intravenous bisphosphonate administration. found were clinically irrelevant as cirrhosis were not seen in these studies Methods A comprehensive literature review was performed using the Mesh where the MTX dose could be lowered in case of AST/ALT elevation; using headings bisphosphonates, inflammation, and atrial fibrillation. Two separate ALT alone would detect (sensitivity) 89,5% of all elevated AST and/or ALT literature reviews were subsequently performed, the first using the Mesh paired results; mean AST and total number of elevated AST before biopsy headings bisphosphonates and inflammation and the second using atrial fib- correlate with histologic grade. MTX does not cause pulmonary fibrosis; No rillation and inflammation. test can predict hypersensitivity pneumonitis. 1 study showed increased Results Literature sources were Medline, Embase, and Cochrane Central. severe MTX toxicity with estimated creatinine clearance < 78.7 mL/min. The initial search using all 3 Mesh headings revealed a total of 3 abstracts, There were no studies addressing hematologic safety monitoring for MTX. however they were not relevant. The subsequent two literature searches gen- Contraindications: We retrieved 1214 citations of contraindication for MTX; erated a total of 269 abstracts and yielded the following insights. AF, 52 met our inclusion and exclusion criteria and were included for data extrac- although once felt to be an electrical problem, is increasingly being viewed as tion. Frequent exclusions in published RCTs are: significant renal disease, an inflammatory condition associated with important structural changes. presence of hepatic disorder, WBC < 3.0 and/or Platelets < 100, Age > 70, Patients with AF have increased levels of inflammatory markers while their past or present malignancy, pregnancy or no use of contraception, history of atrial biopsies consistently show inflammatory changes. Anti-inflammatory alcohol/drug abuse and presence of infection. agents including steroids, polyunsaturated fatty acids, statins, and ACE Conclusion Lowering MTX dosage in case of AST/ALT elevation prevents inhibitors have all been shown to reduce the burden of AF. the development of cirrhosis. No pulmonary monitoring can predict hyper- Bisphosphonates, in addition to their principle mechanism of action on the sensitivity pneumonitis. In the different clinical trials, we find little agreement osteoclast, have multiple other effects on the body. The more potent nitrogen between authors as for MTX exclusion criteria. containing bisphosphonates, termed aminobisphosphonates, have been shown to have pro-inflammatory effects. The acute phase reaction, denoted by fever 133 and influenza like symptoms, experienced by patients following intravenous CANaDian Evaluation of Low DosE Infliximab in Ankylosing administration of aminobisphosphonates reflects the activation of a subset of Spondylitis (CANDLE) T-cells, termed gamma delta T-cells (γ/∂ T-cells). Studies have demonstrated Robert Inman (University of Toronto), Kam Shojania (Arthritis Research proliferation of γ/∂ T-cells and increased cytokine levels in response to amino- Center), Ed Keystone (University of Toronto), Boulos Haraoui (Institut de bisphosphonate administration. The mechanism has been shown to be medi- Rheumatologie de Montreal), Chad Mitchell (Schering-Plough), Walter ated indirectly through inhibition of farnesyl pyrophosphate synthase (FPPS), Maksymowych (University of Alberta) an enzyme within the mevalonate pathway. Inhibition of FPPS results in accu- Objective This study evaluated the efficacy and safety of a low dose inflix- mulation of upstream metabolites, in particular isopentenyl-5-pyrophosphate imab (3mg/kg) in patients with active Ankylosing Spondylitis (AS).

Downloaded on September 27, 2021 from www.jrheum.org Methods This was a randomized, double-blind, multi-center, placebo-con- educational intervention, designed to increase the capacity of primary health trolled phase IIIb study of Infliximab (IFX) versus Placebo (PBO). Subjects care teams to apply best practices to manage arthritis. > 18 years old with active AS (BASDAI ≥ 4) who had an inadequate response Methods The multi-faceted intervention consisted of 30 accredited work- to standard treatment were enrolled. Subjects were randomized to receive IFX shops across Canada for primary health care team members (physicians, nurse 3mg/kg or PBO intravenously at week 0, 2 and 6. The primary endpoint was practitioners, etc.) in non-fee-for-service settings on osteoarthritis (OA) and the proportion of Ankylosing Spondylitis ASsessment responders (ASAS 20) rheumatoid arthritis (RA). Content integrated arthritis best practices adapted at week 12. After week 12, the blind was broken and the original IFX group from published arthritis guidelines and included educational materials for continued to receive 3 mg/kg of IFX every 8 weeks up to week 46 whereas patients and providers and 6-months follow-up reinforcement for providers. the original PBO group initiated 3 mg/kg of IFX at week 16, 18, and 22 25 of 196 participating sites consented to take part in the evaluation of the the (induction period) and every 8 weeks thereafter up to week 46. Final evalua- intervention on patient outcomes. Questionnaires were mailed to patients with tion of both groups was performed at week 50. The IFX dose could be opti- a recorded diagnosis of OA or RA pre-intervention and at 6 and 12 months mized to 5 mg/kg at week 22 or 38 if the BASDAI was > 3 and if there was after the workshops. Appropriate t-tests, and bivariate and multivariate analy- < 50% decrease in BASDAI from baseline. ses were performed. Results 76 subjects (37 PBO and 39 IFX) were randomized into the study. Results Questionnaires were completed by 931, 567, and 370 patients, Subject demographics were similar in PBO/IFX groups with mean (SD) time respectively, at baseline and 6 and 12 months, with 370 patients completing since AS diagnosis being 11.1 (10.3)/11.7 (10.6) years, 73%/72% positive for questionnaires at all three time points. Three-quarters of patients were female, HLA-B27, 11%/8% for history of inflammatory bowel disease and 35%/33% mean age of 66 years. Respondents who answered at all 3 time points were reporting uveitis. 53.8% of subjects in the IFX group achieved the primary slightly younger, reported slightly less pain and disability, had better self- endpoint (ASAS 20) at week 12 compared to 30.6% in the PBO group (P= reported health and less fatigue than non-respondents (p<0.05). There were no 0.042). The ASAS 40, 50 and 70, and ASAS 5/6 responses for subjects in the statistically significant changes across time in best practice recommendations, IFX group were significantly better than those on PBO at week 12. At week referrals or seeing a rheumatologist, surgeon, or physiotherapist. However, 22 and week 50, placebo subjects on open-label IFX had a significant reduc- there was a statistically significant increase in seeing other heath profession- tion in ASAS 20, 40, 50, 70 and BASDAI, BASFI, and BASGI scores compa- als (occupational therapist, social worker, or dietician), and in provision of rable to subjects originally assigned to IFX. At week 38, 67% PBO and 84% community contact information. Patients reported significant increases IFX subjects (p=NS) required dose optimization. 8 patients presented with (p<0.05) in engaging in exercise, including stretching/mobility/ strengthening serious adverse events; 5 PBO-treated subjects and 3 IFX-treated subjects. activities, walking and other types of aerobic activity (e.g. swimming, bicy- Conclusion Low-dose IFX at 3 mg/kg was effective in reducing the signs and cling). While there were no significant changes in pain, fatigue, self-reported symptoms of active AS and was generally well tolerated in subjects. health or disability (HAQ), an increase in amount of exercise was associated with less deterioration in disability; those who did not exercise or decreased 134 exercise were more likely to worsen than those who did not change their ACTH Should Be the First-Line Management in Patients with amount of exercise (p<0.05). Polyarticular Gout and Have Multiple Medical Conditions Conclusion Evaluation of the impact on arthritis patients receiving care from Debra Dye-Torrington (University Of Toronto, Toronto), Sharon Koren these teams showed a significant increase in the proportion exercising, which (Sunnybrook Health Sciences Centre, Toronto), Mary Bell (Sunnybrook in turn was associated with less deterioration in disability over 1 year. Health Sciences Centre, Toronto) Objective To evaluate safety and effectiveness of corticotrophin in the man- 136 agement of patients with acute gout, who are of advanced age and/or have Screening for Psychological Distress in Patients with Psoriatic Arthritis – comorbid diseases. A Validation Survey of the PsAQoL in Canada Methods Literature search was performed on Medline with key index terms: Elyse Reim (Sunnybrook Health Sciences Centre, Toronto), Sarah Gardhouse gout, ACTH, corticosteroids, NSAIDS geriatric management. We developed (Sunnybrook Health Sciences Centre, Toronto), Mary Bell (Sunnybrook a polyarticular gout management protocol with the assistance of our drug Health Sciences Centre, Toronto) information center for use in this special population of patients. The protocol Objective To assess the extent to which psychosocial distress was evaluated includes: 1. an initial dose of 40-80iu corticotrophin intramuscular with in people with Psoriatic Arthritis (PsA) attending one academic rheumatolo- Colchicine 0.6mg b.i.d as first line therapy in patients with heart failure. 2. gist at Sunnybrook HSC as well as exploring the need for new measurement Would repeat this course once if there is inadequate response. tools. Results We found that the patients treated with ACTH got a dramatic Methods Retrospective chart audit on 25 patient charts from a single practice improvement in their symptoms within 8- 48 hours. Few patients needed a Rheumatology clinic at Sunnybrook Health Sciences Centre. Information was second dose of ACTH. abstracted from the clinic chart using a PsA specific chart abstraction tool. Conclusion ACTH in combination with colchicine, is effective in the man- Data abstracted included demographic information (age, gender), personal agement of patients who present with acute gouty attacks, and who have mul- information (martial status, family history), disease duration and measure- tiple medical comorbidities. This management effect has fewer adverse ments of disease severity, current drug therapy (psychotropic and other), other effects, and a more rapid onset of action than indomethacin. This regimen therapies or treatments and date of questionnaire completion. Qualitative data should be considered first line in patients with multiple comorbidities. was extracted from physician’s notes and observations. Results 25 charts were audited; 14 female, 11 male. Age range: 30 - 82 years 135 (mean 49.7); disease duration: one to 32 years (mean 10.3). No charts indi- Evaluation of a National Community-Based Educational Intervention to cated family history of psychosocial distress, though 80% documented fami- Improve Primary Health Care Management of Arthritis: Impact on ly history of severe disease or illness. Disease activity, as defined by morning Patients stiffness, swollen and tender joint count and bilateral grip strength, was regu- Elizabeth Badley (Arthritis Community Research & Evaluation Unit, Toronto larly recorded in 84%. Each measure was documented on the majority of the Western Research Institute, Toronto), Sydney Lineker (The Arthritis Society, patient’s clinic visits. Tender joints 0 – 26, baseline mean 2.5 (n=20). Swollen Toronto), Paula Veinot (Arthritis Community Research & Evaluation Unit, joints: 0 – 12, baseline average 1.5 (n=19). Morning stiffness: 0 minutes - 5 Toronto Western Research Institute, Toronto), Kunyong Xu (Arthritis hours, baseline average 39.5 minutes (n=15). Baseline averages for right and Community Research & Evaluation Unit, Toronto Western Research Institute, left grip were 221.7/20 mmHg and 148/20 mmHg, respectively (n=18). Skin Toronto), Mary Bell (Sunnybrook Health Sciences Centre, Toronto) involvement was not recorded for any patient using a PASI or BSA at any Objective To evaluate the patient outcomes of a national community-based time. All patients had extensive lists of current drug therapies of which only

Downloaded on September 27, 2021 from www.jrheum.org 24% were on psychotropics. Most patients had experienced other forms of potentially more severe inflammatory arthritis. In RA, serially determined therapy (consults, aids, referrals).Two patients had seen a psychiatrist for CCP may predict erosive disease and CCP titers change with treatment in depression counseling and two other patients had been seen by social work- some but not all studies. We sought to determine if CCP status changed in ers. Patient self assessment questionnaires were not completed regularly by subjects with inflammatory arthritis and whether changes associated with all patients and no patients had ever completed a PsA specific questionnaire clinical outcomes. (PsAQol, PDI, IPSQ, or PLSI). Physician’s notes for the majority of patients Methods Subjects with inflammatory arthritis of less than 12 months duration indicated periods of physical or emotional distress related to life events (mis- (n=50; undifferentiated arthritis (UA), rheumatoid arthritis (RA) and other carriages, illness of family member, and change in employment) but only 25% arthropathies (O)) were followed for up to 58 months. Clinical features of patients had record of seeking treatment for this distress. including rheumatoid factor, disease activity (DAS3CRP), functional status Conclusion This audit demonstrates the need for better evaluation of psy- (mHAQ), and the presence of erosions were recorded. Antibodies to CCP chosocial distress in patients with PsA. A larger study looking to validate the were assessed in serial blood samples (2-5 samples/subject) using ELISA. use of PsAQoL in a Canadian cohort is now planned. Results At first visit, the majority of RA patients were CCP +ve and the majority of UA patients were CCP -ve. The majority of subjects did not 137 change CCP status (persistently CCP -ve n=9; persistently CCP +ve n=24). Case Report: Successful Treatment of Refractory Psoriatic Achilles CCP status changed in 17 subjects (7 positive to negative; 10 negative to pos- Tendinitis with Prolotherapy itive including 2 subjects with UA that evolved into RA). Patients that Neil Desai (St. Paul’s Hospital Orthopaedic Medicine Clinic), Alice V. remained CCP +ve and those that had higher mean CCP titers during follow- Klinkhoff (University of British Columbia), Jean H. Gillies (University of up were less likely to attain clinical remission (DAS3CRP<2.6). Titers of British Columbia) CCP fluctuated over time but correlated poorly with RF titers and disease Objective We describe the successful treatment of refractory psoriatic activity and did not correlate with mHAQ. Erosions at one year were not Achilles tendinitis with prolotherapy. more common in patients persistently CCP positive. Methods A 37 year old man developed psoriatic arthritis in 2000. MSK Conclusion CCP measurements were stable in the majority of patients. A examination revealed oligoarthritis [left wrist, left knee, and left ankle], minority of CCP-ve UA patients who seroconverted evolved into RA sug- dactylitis [left middle finger], and right Achilles tendinitis. Treatment includ- gesting a possible role for repeat CCP testing however these subjects did not ed left knee joint and left middle finger flexor tendon sheath steroid injec- have a poorer clinical outcome. tions, flurbiprofen [400 mg/day] and sulfasalazine [3 gm/day]. The oligoarthritis and dactylitis resolved, but he continued to have severe right 139 Achilles tendinitis. He was unable to work as a meat cutter. Walking was lim- New Onset Of Inflammatory Polyarthritis in a Patient on Adalimumab ited to 12 blocks. Methotrexate [22.5 mg SC weekly] was of no benefit. Monica Lee (University of Toronto), Rima Petroniene (The Royal Victoria Steroid injections given on three occasions in 2002 into the Achilles enthesis Hospital), Carter Thorne (The Arthritis Program, Southlake Regional Health were of no benefit. An MRI in May-2003 revealed thickening and increased Centre) signal of the Achilles tendon, a small amount of high signal in the region of Objective To describe a case of new onset inflammatory polyarthritis associ- the pre-Achilles bursa, and a calcaneal spur. In May 2003 he received a series ated with the use of adalimumab in the treatment of Crohn’s disease. of three prolotherapy injections at two weekly intervals, using a 15% dextrose Methods Case report solution into the Achilles attachment on the calcaneus, to the fasciial reflec- Results A 64-year-old woman with a 10-year history of Crohn’s disease, pre- tion of the Achilles insertion, and to calcaneal attachment of the right plantar sented with a new onset of symmetrical polyarthritis while being treated with fascia. adalimumb. Previous disease treatment of Crohn’s included oral budesonide, Results Two weeks following the first prolotherapy injections, he reported a prednisone, 5-aminosalicylic acid, and azathioprine. Her past medical history 95% subjective improvement: he had no pain at rest, with pain only precipi- was significant for bilateral carpal tunnel release 3 years ago. The treatment tated by walking 18 blocks. He was able to stand for an unlimited period. On regimen of adalimumab was 160 mg on day 1, 80 mg on day 15, and 40 mg examination at first inspection, the Achilles and the retrocalcaneal regions every 2 weeks thereafter. After 12 weeks of therapy, the patient developed appeared normal. There was very minimal swelling involving the right retro- acute severe muscle pain in the upper and lower extremities. She denied mus- calcaneal region. Palpation of the right retrocalcaneal region was entirely cle weakness. Joint swelling was reported as “absent”, but she had some pain-free. There was minimal swelling of the right Achilles tendon on palpa- “joint pain”. There were no associated fevers. Laboratory tests showed a pos- tion. He received two more prolotherapy injections at two-weekly intervals. itive ANA of 1:160, rheumatoid factor of 8 kIU/L, CRP of 11 mg/L, ESR of Two weeks following the third and final prolotherapy injections, he reported 15 mm/hr, and haemoglobin of 125 g/L. Platelet count and liver function tests a subjective 95% improvement, his only limitation being intermittent mild were normal. Her adalimumab was discontinued immediately. She described heel pain precipitated by sitting for one hour, the pain immediately resolving her Crohn’s condition to be well-controlled while on therapy. After discontin- with a change of posture. He reported he was able to stand and walk for an uation of therapy, the patient continued to have “severe muscle discomfort” unlimited period. Examination of the right Achilles region was entirely nor- and was referred to a rheumatologist for assessment. On examination, she had mal. He was able to return to work. There has been no recurrence of the palmar erythema, which the patient reported as long-standing. A general sys- Achilles tendinitis. tem examination was unremarkable. No skin lesion of psoriasis nor Conclusion This is the first case report of psoriatic arthritis involving enthe- hepatosplenomegly was noted. Articular examination revealed no morning sitis responding to prolotherapy. stiffness. Grip strength was 180/170, right handed. Active joint count included 40 tender, with 14 swollen joints. The swollen joints were in the small 138 joints of both hands, both wrists, right elbow with a 20 degree flexion defor- Clinical Utility of Serial Measurement of Antibodies to Cyclical mity, both knees with a bulge sign, and stress pain in the ankles. Decrease Citrullinated Peptides in Early Inflammatory Arthritis range of motion of both shoulders was noted. Her power was limited, by pain. Daniela Stroescu (University of Manitoba), Irene Smolik (University of Her presentation was consistent with an systemic (autoimmune) inflammato- Manitoba), Keng Wong (University of Manitoba), David Robinson ry arthritis. The patient was initiated on intra-articular corticosteroid and (University of Manitoba), Christine Peschken (University of Manitoba), methotrexate for the management of her inflammatory arthritis. Hani El-Gabalawy (University of Manitoba), Carol Hitchon (University of Conclusion To our knowledge, this is the first case report of new onset Manitoba) inflammatory polyarthritis associated with the use of TNFi, adalimumab. Objective Antibodies to cyclical citrullinated peptide (CCP) precede the Psoriasis induced by anti-TNF agents has been reported in the literature. onset of rheumatoid arthritis (RA) and assist in identifying patients with There has also been a case series describing exacerbation of rheumatoid

Downloaded on September 27, 2021 from www.jrheum.org arthritis in 3 patients who were treated with infliximab therapy. The mecha- physician global assessment) and specific disease characteristics (frequency nism of these paradoxical adverse effects of anti-TNF agents is unclear. of Raynaud’s episodes, diffuse versus limited status, tender joint count, 140 inflammatory muscle disease, GI symptoms, hand and non-hand ulcers, Targeted Inhibition of IL-6 Signaling with Tocilizumab Improves Quality breathing problems and comorbid pain conditions (osteorarthritis, rheumatoid of Life and Function in Patients with Rheumatoid Arthritis with arthritis and back pain) with pain. Inadequate Response to a Range of DMARDs Results The sample was 86.3% female with a mean (SD) age of 55.0 (12.4) J. J. Gomez-Reino (University of Santiago de Compostela, Santiago, Spain), years and mean (SD) disease duration of 10.8 (8.8) years. The overall pro- B. Nair (University of Saskatchewan, Saskatchewan, Canada), M. J. Fairfax posed hierarchical model predicted 36.6% of the variance in pain intensity. (ArthroCare/AC & R PC, Phoenix, AZ), K. Pavelka (Institute of Demographic factors did not significantly contribute to the variance in pain Rheumatology, Prague, Czech Republic), E. Alecock (Roche Products Ltd, (R2 change = 0.01, p=0.151). While socioeconomic variables and general dis- Welwyn, United Kingdom), T. Woodworth (Roche Products Ltd, Welwyn, ease status did significantly predict pain (R2 change = 0.02, p=0.15) and (R2 United Kingdom), M. Genovese (Division of Immunology and change = 0.08, p<0.0001) respectively, specific disease characteristics pre- Rheumatology, Stanford University School of Medicine, Stanford, CA, USA) dicted the largest proportion of variance in pain symptoms (R2 change = 0.26, Objective This study examined the effect of tocilizumab (TCZ), a humanized p<0.001) despite being entered last. Independent predictors of pain included IL-6 receptor antibody, on function and health related quality of life (QOL) in lower education (beta = -0.10, p=0.016), shorter disease duration (beta = - patients with moderate to severe active RA with inadequate response to tradi- 0.09, p=0.041), a higher number of Raynaud’s episodes per week (beta = tional disease-modifying anti-rheumatic drugs (DMARDs). 0.12, p=0.004), a higher tender joint count (beta = 0.20, p<0.001), GI symp- Methods 1216 patients were evaluated in a phase III, randomized (2:1), dou- tom involvement (beta = 0.21, p<0.001), presence of hand ulcers (beta = 0.16, ble-blind, placebo-controlled study. Patients continued stable pre-entry doses p<0.001), more severe dypnea (beta = 0.26, p<0.001) and the presence of a of DMARDs (methotrexate, chloroquine/hydroxychloroquine sulfasalazine, comorbid pain condition (beta = 0.08, p=0.049). leflunomide, azathioprine, or parenteral gold) and received additional TCZ 8 Conclusion Patients with SSc self-report significant pain symptoms. mg/kg or placebo intravenously, every 4 weeks for 24 weeks. Outcome meas- However, SSc is a heterogeneous disease and no prior studies have systemat- ures included Health Assessment Questionnaire (HAQ), Functional ically assessed specific factors related to pain. This study showed that the Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale and majority of explained variance in pain is related to specific symptoms of SSc, the Short Form 36 Health Survey (SF-36). as opposed to general disease severity or socioeconomic factors. Raynaud’s Results Treatment with TCZ resulted in an early significant and clinically rel- episodes, tender joints, GI involvement, hand ulcers, dyspnea, and comorbid evant improvement in all QOL parameters. The improvement in the QOL pain conditions all contribute significantly to pain intensity ratings. parameters correlated with a reduction in disease activity in the TCZ group. Mean changes in HAQ scores showed a clinically relevant improvement at 24 142 weeks with TCZ, -0.47 vs placebo, -0.20 (P <0.0001), with 60.4% vs 33.9% of MRI Evaluation of Scalp Artery Inflammation in Patients with Giant patients achieving a clinically relevant improvement. Improvement in FACIT- Cell Arteritis Fatigue scores with TCZ was observed as early as week 8, with mean changes Samir Patel (St. Joseph’s Healthcare), Nader Khalidi (St. Joseph’s above the minimal clinically important difference (MCID) of 4 points, increas- Healthcare), Ryan Rebello (St. Joseph’s Healthcare) ing to 8.0 by week 24 (vs placebo, 3.6; P < 0.0001). Mean improvements for Objective To evaluate scalp artery inflammation using high field MRI in the individual domain scores of the SF-36 were higher in the TCZ vs placebo. patients with Giant Cell Arteritis (GCA) and to assess the utility of using a Greater improvements in SF-36 physical (PCS) and mental component scores surface coil and fluid sensitive sequences in the detection of the arterial (MCS) were observed in the TCZ group vs placebo: PCS: 8.9 vs 4.1; MCS: 5.3 inflammation. vs 2.3 (P < 0.0001), respectively (MCID = 2.5-5 points). Methods Previous studies have demonstrated the ability to detect scalp arte- Conclusion Treatment with TCZ resulted in significant improvements com- rial wall inflammation in patients with GCA using gadolinium enhanced, high pared with placebo in physical function, fatigue and physical and mental resolution MRI of the entire head. 17 patients diagnosed with GCA (based on health scores. This large phase III study demonstrates that TCZ treatment pro- ACR criteria) were examined by high field (3T) MRI. Gadolinium enhanced vides clinically relevant benefits for patients with RA with an inadequate imaging of the entire brain using a head coil was obtained. In addition, we response to a range of DMARDs. obtained images using a surface coil placed directly over the clinically suspected superficial temporal artery (STA). T1-post gadolinium images and fluid 141 sensitive (T2 weighted) images were obtained using the surface coil. All Socio-Demographic and Clinical Correlates of Pain in Patients with patients also underwent conventional testing including temporal artery biopsy. Systemic Sclerosis (SSc) Results One patient was unable to tolerate examination using the head coil Orit Schieir (McGill University), Brett Thombs (Department of Psychiatry due to headache. Utilizing the head coil, 5/16 (31.3%) patients demonstrated Sir Mortimer B. Davis–Jewish General Hospital, McGill University), Marie MRI evidence of inflammation of the STA or its branches. A larger propor- Hudson (Division of Rheumatology Sir Mortimer B. Davis–Jewish General tion demonstrated signs of STA wall inflammation using the surface coil; 8/17 Hospital, McGill University), Suzanne Taillefer (Division of Rheumatology (47.1%) using the fluid sensitive sequence and 9/17 (52.9%) using the T1- Sir Mortimer B. Davis–Jewish General Hospital), Canadian Scleroderma gadolinium enhanced sequence. MRI demonstrated involvement of arteries Research Group (CSRG), Murray Baron (Division of Rheumatology Sir other than the STA in 7/17 (41.2%) patients. The contralateral STA was Mortimer B. Davis–Jewish General Hospital, McGill University) inflamed in 2, the occipital arteries in 2, both the contralateral STA and occip- Objective To assess the socio-demographic and clinical correlates of pain in ital arteries in 1 and the cavernous carotid artery in 2. All but 1 of these a Canadian community based cohort of patients with systemic sclerosis (SSc). patients had concomitant involvement of the ipsilateral STA. The average Methods 408 patients with SSc diagnosed by a rheumatologist were recruit- length of STA biopsied was 3.0 cm. Biopsy was positive in only 2/17 (11.8%). ed from 15 rheumatology centers affiliated with the Canadian Scleroderma Of these, MRI evidence of inflammation was present in the STA in 1 and the Research Group (CSRG). Registry patients annually provide a detailed clini- other demonstrated isolated inflammation of the cavernous carotid artery. cal history, undergo a medical examination and complete a self-report battery Conclusion In patients diagnosed with GCA, high field MRI is a useful of demographic variables and SSc outcome measures including a numerical adjunct, demonstrating MRI evidence of inflammation of the STA in 52.9% rating scale (NRS) of pain intensity. The present study analyzed cross-sec- of patients. This compares quite favorably with temporal artery biopsy which tional data provided by patients at baseline. Hierarchical linear regression was was positive in only 11.8% of cases. Both biopsy positive cases demonstrat- used to assess the relative associations of demographic (age, sex), socioeco- ed MRI evidence of arterial wall inflammation. These findings suggest that nomic (education, marital status) general disease status (disease duration, MRI may be able to supplant temporal artery biopsy in the assessment of

Downloaded on September 27, 2021 from www.jrheum.org patients with GCA. Imaging using the surface coil with gadolinium yields the several comments have suggested that more teaching on physical examina- highest rate of detectable arterial wall inflammation. tion, infiltration techniques and musculoskeletal anatomy would be benefi- cial. Also, externs and residents seem to indicate by their comments that they 143 would appreciate more teaching on long term follow up of patients with Case Report: 19 year old Female with SLE Developing Rapidly chronic diseases. Worsening Cardiomyopathy Conclusion The initiatives put in place are helpful in motivating externs and Thiru Singam (University of Saskatchewan), Regina Taylor-Gjevre residents during the rotation. The information gathered by the end of rotation Systemic lupus erythematous (SLE) usually affects women of reproductive questionnaire represents a useful tool to keep improving the quality of the age. Pregnancy and its outcome is a major concern to most SLE patients. rotation. These measures could contribute to increase the number of appli- Cardiomyopathy may occur with the flare of SLE, which is an autoimmune cants who choose rheumatology as a career. disease with varying presentations. A 19 year old Aboriginal female was diagnosed with SLE at the age of 12 145 with diffuse glomerulonephritis requiring hemodialysis (HD) for 4 years and Unusual Manifestations of Ulcerative Colitis in a 34-year-old Man subsequent full renal function recovery and positive antiphospholipid syn- Sabrina Fallavollita (McGill University), Christian Pineau (McGill drome. She presented to the hospital with sudden onset of pleuritic chest pain University), Michael Starr (McGill University) and dyspnea, which worsened by lying flat and improved by leaning forward. We present the case of a 34 year old Jamaican male, with ulcerative colitis She reported nausea and vomiting during this episode and had flu-like symp- (UC) and arthropathy, who developed ischemia of his toes six weeks into a toms a few days prior. Patient had delivered a baby boy via cesarean 3 months flare of his UC. prior. Prior to hospitalization, the echocardiogram revealed an ejection frac- He presented with 3 days of progressive burning foot pain not relieved by rest tion (EF) of 43%. Subsequently, the echo revealed an EF of 27% with severe or analgesia. He had also had increased bloody bowel movements, a 5 kg global hypokinesis with small to moderate pericardial effusion. Patient was weight loss, and bilateral knee swelling and pain. On exam, he was afebrile, diagnosed with renal failure, pneumonia and cardiomyopathy, which were BP 130/80, and pulse was 115 and regular. Respiratory and cardiovascular treated with HD, mycophenolate mofetil, prednisone, metoprolol and valsar- was normal, there were no murmurs and peripheral pulses were present. There tan. Patient developed a deep venous thromboembolism which was treated were no rashes, or peripheral stigmata of endocarditis. Abdomen was soft, and with only aspirin due to issues of compliance. Upon follow-up, a repeat rectal exam showed BRBPR. He had synovitis in his bilateral knees and no echocardiogram revealed rapid improvement in cardiac function and resolu- other active joints. In his feet, his peripheral pulses were present and bound- tion of the pericardial effusion. ing, the toes were cold and blue to varying degrees, and there was significant SLE is a disease which may affect many organs leading to dysfunction and soft tissue edema bilaterally. Pain was out of proportion to physical findings. eventually death. Pregnancy causes major flares and life threatening organ Investigations including CBC, Cr, LFT’s, Urinalysis, INR, CXR, and blood dysfunction but the disease is usually quiescent after delivery. This patient cultures were normal. Angiogram of the lower extremities did not show dis- was found to have relapse of renal failure along with rapid development of ease proximal to the small vessels of the toes. Echo and imaging of the bowel cardiomyopathy. Presence of antibodies from pregnancy along with the addi- was normal. Autoimmune work up including ANCAS, ANA, and antiphos- tion from SLE antibodies may have induced cardiomyopathy. This patient is pholipid antibodies were negative. Hypercoagulable work up revealed an also predisposed to thromboemboli due to hypercoagulable states of pregnan- acquired Protein C deficiency with a level of 0.24. Biopsy of an affected toe cy, SLE antibodies and stasis of blood due to left ventricular dysfunction. For revealed vasculopathy with extensive ischemic changes and necrosis and no a patient with numerous organ dysfunctions, such as this, chances for clinical evidence of vasculitis. improvement are good if diagnosed and treated promptly. A hypercoagulable state in patients with Ulcerative Colitis has been well described. Venous events are more common than arterial. Digital ischemia in 144 the setting of an acute flare of ulcerative colitis had previously been described Teaching Strategies — Clinician-Teacher Award but the mechanism was unknown[1]. A mechanism involving digital ischemia Patrick Liang (Université de Sherbrooke) and acquired Protein C deficiency will be discussed. Objective To improve teaching of fundamentals of rheumatology to externs 1. Chaun, H., et al. Ischemic skin lesions in ulcerative colitis. Can Med Assoc and internal medicine core curriculum residents; to popularize the rheumatol- J 1985;132: 937-9. ogy rotation and augment its visibility amongst externs and residents. Methods Within the context of the Clinician-Teacher award granted by The 146 Arthritis Society, initiatives developed during the last 2 years include: 1) a A Prospective Study of Multidimensional Fatigue in Patients with series of lectures covering essentials of rheumatology, that cycles every 8 Spondyloarthropathy weeks. This corresponds to the average duration of the rheumatology rotation D. DaCosta (McGill University Health Centre), M. Zummer (Hôpital for internal medicine residents; 2) Rotation objectives have been reshaped to Maisonneuve-Rosemont), M.A. Fitzcharles (McGill University Health Centre) reflect expected clinical competencies; 3) pre tests and post tests are given to Objective To examine the course of fatigue in patients with spondy- every candidates during the rotation; 4) clinical vignettes published on the loarthropathy (SpA) using a multidimensional assessment and to elucidate rheumatology unit’s web site every month, which externs and residents discuss longitudinally the relative contribution of disease-related, behavioural and among themselves or with the rheumatology fellow, prior to review with teach- psychosocial variables to physical and mental dimensions of fatigue. ers; 5) an appreciation questionnaire is completed at the end of the rotation. Methods Ninety-seven patients with SpA completed the following battery of Results Questionnaires have been distributed since the last year. The follow- standardized questionnaires twice during a 12-month interval: ing results describe that period. Thirteen questionnaires out of a possibility of Multidimensional Fatigue Inventory (MFI-20), sleep quality (Pittsburgh Sleep ~ 35 were returned. Teaching activities are much appreciated; learning objec- Quality Index- PSQI), depressed mood (Center for Epidemiological Studies- tives are found useful. Pre and post tests: most agree, or strongly agree that Depression Scale), social support ((SSQ-6), leisure time physical activity they are helpful in identifying strengths and weaknesses. Although appreciat- (Aerobics Center Longitudinal Study Physical Activity Questionnaire), dis- ed, externs/residents have mentioned that they would be interested in a more ease activity (BASDAI), and functional ability (BASFI). A series of multi- formal feedback. The clinical vignettes are very popular, and the majority of variate regressions were computed to identify contributors to physical and respondents to the questionnaire strongly agree that this feature is helpful in mental fatigue. stimulating their learning. An added value to the end of rotation questionnaire Results Patients scored high on all five MFI-20 fatigue dimensions, with gen- is that it provides rapid and honest feedback, as it is anonymous. Gathered eral fatigue and physical fatigue having the highest scores. Comparisons of information should help in constant improving of the rotation. For example, mean MFI-20 subscales across both assessments indicate that fatigue across

Downloaded on September 27, 2021 from www.jrheum.org the various dimensions remained stable during the 12-month study period. study entry significantly associated at the bivariate level with greater mental Physical fatigue at baseline was strongly associated with physical fatigue at fatigue at the 12-month follow-up were not working, greater disease activity, the 12-month follow-up (r=.72, p<.001). Additional variables collected at poorer functional capacity, higher depression, greater stress levels, poorer study entry significantly associated at the bivariate level with greater physical sleep quality, and less self-efficacy to manage SpA. The results of the second fatigue at the 12-month follow-up were older age, not working, longer disease model found higher mental fatigue at study entry (p<.0001) and poorer self- duration, greater disease activity, poorer functional capacity, higher depres- efficacy to manage SpA (p=.001) to be significant independent determinants sion, greater stress levels, poorer sleep quality, less self-efficacy and less par- of mental fatigue at the 12-month follow-up. ticipation in exercise. The final regression model examining predictors of Conclusion Fatigue was relatively stable over the 12-month study period high- physical fatigue at the 12-month follow-up showed that the study entry vari- lighting the need to develop and evaluate interventions aimed at ameliorating ables that remained significant determinants were baseline physical fatigue this potentially chronic symptom. These findings suggest that improving sleep (p<.0001), being female (p=.034) and poorer sleep quality (p=.03). Mental and enhancing self-efficacy to manage illness may be important areas to Fatigue at study entry remained moderately associated with mental fatigue at address in interventions aimed at improving fatigue in this patient population. the 12 month follow-up (r =.63, p<.001). Additional variables collected at

AUTHOR INDEX Bingham C, 49 Conner Spady B, 110 Fitzgerald A, 24 Bissonnette B, 46 Conner-Spady B, 99,107 Fleischmann R, 73 Abu-Hakima M, 2 Bobba R, 122,128 Connors S, 68 Fortin P, P3,108,120 Adachi J, 54,57,89 Boers M, 28 Constantine G, 54,57 Franklin J, 27,29 Agarwal S, 31 Bogoch I, 119 Cooper S, 73 Friedlich M, 91 Al Zahraly Z, 102 Boire G, 8,90,121 Cornet P, 18,21 Fritzler M, 36,79 Albert L, 92 Bolster L, 44 Cossette P, 8 Froese W, 109 Alecock E, 45,47,140 Bombardier C, 75,77,78,80,81, Courteau J, 111 Furst D, 31 Aletaha D, 60 84,85,116,132 Cravets M, 39 Gandhi M, 20,25 Allard-Chamard H, 3 Bonventi G, P3,108 Crawford A, 13,61 Gardhouse S, 136 Alten R, 30,45 Boonen A, 99,110 Crystal E, 131 Garneau P, 65 Ammendolia C, 69 Bostwick J, 12,97 Csrg C, 2 Garner S, 90 Appenzeller S, P5,11 Boulos P, 122,128 Czarnecka K, 87 Gelber A, 22,57 Aranda R, 18,19,21,25 Boyle E, 66,69 Da Silva N, 47 Genovese M, 25,39,47,140 Ardern R, 48,53 Branson H, 38 Dacosta D, 1,146 Gibbs L, 33 Armstrong D, 38 Brasington R, 60 Daniel L, 1 Gillies J, 137 Askling J, 27,29 Breton D, 65 Danoff S, 22 Gillis M, P1 Atkins C, 30 Brown J, 34,35,47 David T, 1 Gladman D, Averns H, 9,10 Burmester G, 39 Davison K, 34,35 P3,P4,41,42,63,103,105,108,117, Badley E, 135 Butany J, 1,5,39,50,90,93, De Brum-Fernandes A, 3,8,57,111 120 Baer P, 7 94,123,125 De Vita S, 60 Goldberg R, 103,105 Bahrami A, 89 Cabana F, 121 Decoster C, 24 Gomez-Reino J, 47,140 Baillargeon J, 4 Cai Y, P3 Delmas P, 54 Graydon S, 17,32 Baldassare A, 73 Caines A, 70 Desai N, 137 Greenwald M, 39,49,60 Baranci M, 34,35 Carette S, 98 Dhindsa N, 109 Grouchy B, 62 Barnabe C, 55,112,113 Carmona R, 98,114 Dieude M, P1 Guerette B, 42 Baron M, 2,43,76,79,82, Carrier N, 8 Dixit S, 64 Guillemin F, 123,125 102,104,141 Catton M, 71 Docherty P, 2 Haaland D, 89 Barr S, 112,113,130 Cepoiu M, 24 Dodge G, 88 Hagerty D, 39,73 Barra L, 74 Chan D, 122,128 Dougados M, 18,19,20,21,39,73 Hall R, 40 Bassel M, 43 Chandran V, P4,5,117 Dufort P, 3 Halliday W, 38 Bathon J, 73 Cheng C, 5,50,94 Duval N, P2 Hamilton S, 53 Bautista L, 48,53 Cheung R, 88 Dye-Torrington D, 134 Haraoui B, 46,49,52,59,116,133 Bayoumi I, 122,128 Chines A, 54,57 Edworthy S, 90 Hart D, 109 Beattie K, 97,122,128 Choquette D, 46,67 El-Gabalawy H, 36,55,109,138 Hasek-Watt M, 58 Beaudet F, 46 Choy G, 88 Elbers J, 38 Hawkins C, 38 Beaulieu A, 45 Christiansen C, 54,57 Elias B, 36 Heale C, 62 Beaulieu M, 34,35,121 Christopher-Stine L, 22 Emery P, 19,31,49,73 Henderson J, 90 Becker H, 18 Chubick A, 73 English J, 77,78,84 Hessey E, 60,73 Becker J, 19,20,21,25 Churchill D, 89 Esdaile D, 58 Hitchon C, 55,138 Bell M, 88,119,123,125,131,134, Cibere J, 16 Fahlman N, 13,61 Hochberg M, 27,29 135,136 Ciesielska M, 54 Fahmi H, P2 Hoeck H, 54 Bélisle P, P5 Ciubotariu E, 52 Fairfax M, 140 Homik J, 21 Benseler S, 38 Ciurea I, 77,78 Fallavollita S, 145 Horton M, 22 Bensen W, 67 Cividino A, 12,60,84,97,122,128 Fan X, 76 Hsu W, 69 Berman A, 18,21 Clarke A, P5,11,124, Faraawi R, 67 Hudson M, 2,43,79,82,104,141 Bernatsky S, 2,11,124 Codding C, 18,21 Ferland D, 65 Huizinga T, 36 Bernstein J, 79 Cohen S, 39 Ferracioli G, 31 Hummers L, 23 Bessant J, 34,35 Colin B, 8 Filipow P, 127 Humphrey-Murto S, 91,92,96 Bessette L, 18,21,34,35 Connelly D, 33 Fitzcharles M, 146 Hutchinson C, 38

Downloaded on September 27, 2021 from www.jrheum.org Ibanez D, 41,103,105,120 Lubovich A, 108 Poirier N, 121 Taillefer S, 43,104,141 Inman R, 63,66,69,127,133 Lucero M, 30 Pope J, 2,56,70,71,72,73, Tam W, 16 Ioan-Facsinay A, 36 Luggen M, 25 74,76,83,84,86,100,102 Tenenbaum J, 1 Ioannidis G, 122,128 Lundon K, 101 Pritzker K, 89 Taylor-Gjevre R, 40,44,143 Islam K, 53 Lupton T, 13,61,109,130 Provost Y, 1 Theoret J, P1 Jamal S, 87 Macdonald H, 92 Rahman P, 48,53,63 Thomas D, 90 Jean S, 34,35 Magrini F, 49 Rahme E, 46 Thombs B, 43,79,82,104,141 John S, 114 Maksymowych W, 63,99,106, Ramos-Remus C, 30 Thompson A, 17,32,70 Johns C, 13 107,110,127,133 Rauch J, P1 Thomson J, 90 Johnson N, 13,61 Malenfant D, 71 Raynauld J, 46 Thorin E, P1 Jones N, 2 Maly M, 33 Rebello R, 142 Thorleifson M, 95 Joseph L, P5 Markland J, 2,36,90 Reim E, 136 Thorne C, 84,116,139 Joshi C, 14,19,20,25 Martel-Pelletier J, P2 Rich E, 46,59 Tin D, 148 Katchamart W, 80,81 Martin L, 68,112,113,130 Roberts J, 131 Toes R, 36 Kavanugh A, 60 Masetto A, 4,93 Robindaine J, 121 Toloza S, P4,120 Kean W, 122,128 Mathieu J, 2,65 Robinson D, 2,36,55,95,138 Tony H, 60 Keeling S, 107 Matsos M, 26,98 Rogers P, 115 Touchie C, 91,96 Keiserman M, 18,21 McCallum R, 122,128 Rohekar G, 56 Touma Z, 120 Kendler D, 54 Mcilroy J, 101 Rosen C, P4,117 Tran A, 14,37 Kevin F, 49,73,93,116,129,133 Mckay J, 47 Roslin N, 63 Troung N, 65 Khalidi N, 2,26,64,92,98,114,142 Mckendry R, 37 Rovensky J, 30 Troyanov Y, 46 Khraishi M, 31,62,116 Mehta S, 83 Rowe K, 31,49 Trudeau J, 132 Kiefer K, 61 Menard C, 4 Rubbert-Roth A, 45 Tse S, 66 Kirschner Q, 58 Ménard H, 8,36 Russell A, 19,20,25,107 Tugwell P, 28,80,123,125 Kiss A, 123,125 Meng M, 27,29 Saldate C, 18,21 Tulloch-Reid D, 41,120 Klinkhoff A, 137 Merhi Y, P1 Salliot C, 75 Uddin M, 53,63 Knoll G, 96 Mierdel S, 148 Salonen D, 69,127 Udell J, 31 Koehler B, 6 Miettunen P, 13,61 Samadi N, 70 Ueng J, 117 Koehler M, 6 Miller P, 54 Sandhu S, 119 Unnithan T, P3,108 Koehn C, 58 Milman N, 15 Schabort I, 122,128 Urowitz M, P3,41,57,103, Koren S, 134 Mironyuk L, 50 Schachna L, 99 105,108,120 Kraag G, 15,90 Mitchell C, 133 Schentag C, P4,117 Van der Heijde D, 75 Kraishi M, 67 Mittoo S, 22,23 Schieir O, 141 Van Vollenhoven R, 31,49 Kremer J, 1,5,19,25 Moreland L, 19,49 Schiff M, 18,21 Vanasse A, 111 Kuriya B, 1 Morency N, 46,59 Schneider R, 101 Veinot P, 135 Kvien T, 39 Mugford G, 62 Senecal J, 46,59 Venditolli P, 65 Kwan Tat S, P2 Mulpuru S, 96 Setty Y, 48,53 Villela R, 100 LaBrie N, 61,129 Mysler E, 47 Shanmugarajah S, P4,117 Vinet E, P5,124 Lacaille D, 27,29,115 Nair B, 140 Shaw T, 39,31 Wagner B, 49 Lajeunesse D, P2 Nantel F, 67 Shea B, 80 Walker R, 40 Lambert D, 121 Nasonov E, 47 Sherrer Y, 20 Waltin-James J, 116 Lambert R, 127 Nayiager S, 18,21 Shojania D, 58 Waserman S, 64 Landells I, 62 Newkirk M, 36 Shojania K, 133 Weinberg E, 7 Landolt-Marticorena C, P3,108 Newton E, 82 Shupak R, 57,101 Wells G, 28,123,125 Larrivee L, 121 Nicolson P, 9 Simon T, 27,29 Westhovens R, 19,20,25 Laughlin S, 38 Nikpour M, 105 Singam T, 143 White A, 60 Law G, 72 O’Shea F, 66,69 Smith C, 92 Wigley F, 23 Lawrence E, 102 Obeid J, 122,128 Smitten A, 27,29 Wilkins A, 77,78 Laxer R, 66 Ortiz Z, 80 Smolen J, 30,45,60 Willemze A, 36 Le Page J, 6 Panopolis P, 2 Smolik I, 138 Wise R, 23 Lechtzin N, 22 Papaioannou A, 122,128 Songcharoen S, 18,21 Wither J, P3,108 Leclerc S, 2 Pardy N, 53 St-Pierre A, 46 Wolfe F, 27,29 Leclercq S, 68,90,139 Patel S, 142 Starr M, 145 Wong K, 109,138 Lee P, 1,51 Pavelka K, 140 Ste-Marie L, 34,35 Wong R, 42 Levine J, P1 Payne M, 74 Steele R, 82 Wood J, 33 Lewiecki E, 54 Peddle L, 53,63 Stein J, 1 Wood T, 91,92 Li T, 19,20,21,28 Pekush R, 40 Stroescu D, 138 Woodson G, 54 Li X, 85 Pelletier J, P2,46 Sturge M, 63 Woodworth T, 30,45,140 Liam M, 129 Pellett F, P4,117 Subramanian G, 114 Xu K, 135 Liang P, 4,8,144 Peschken C, 36,55,72,138 Suissa S, 27,29 Yeadon C, 46 Lin C, 18,21 Peterson C, 69,139 Sutton E, 2 Young C, 11 Lindenschmidt R, 95 Pilon D, 111 Sweetser M, 49 Yuen S, 57,86,100 Lineker S, 135 Pineau C, P5,11,124,145 Syrotuik J, 116 Zummer M, 45,65,90,146 Low A, 51

Downloaded on September 27, 2021 from www.jrheum.org Correction Dixit S, Waserman S, Khalidi N. Oral contraceptives and sys - temic lupus erythematosus, current practice in Hamilton [abstract]. J Rheumatol 2008;35:1192. The second author is Sari Herman (McMaster University). We regret the error. doi:10.3899/jrheum.080CRAC1